| 1. |
3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach.
Elgazar AA, El-Domany RA, Eldehna WM, Badria FA
In an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-β-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed to identify the most promising hybrid. Eight compounds exhibited superior anti-inflammatory activity compared to the parent compound. Two of these hybrids ( and ) were able to reduce gene expression of TNF-α in LPS-induced inflammation in RAW 264.7 cells, similar to dexamethasone. Subsequently, the hepatoprotective potential of these hybrids was evaluated against acetaminophen (APAP) toxicity in HepG2 cells at doses of 1 and 10 μM. Both hybrids effectively restored cytokine levels, which had been elevated by APAP, to normal levels. Furthermore, they normalized depleted superoxide dismutase and reduced glutathione levels while significantly reducing malondialdehyde (MDA) levels. Network pharmacology analysis suggested that AKBA-based hybrids exert their action by regulating PI3K and EGFR pathways, activating anti-inflammatory mechanisms, and initiating tissue repair and regeneration. Molecular docking studies provided insights into the interaction of the hybrids with PI3K. Additionally, the hybrids demonstrated good stability at different pH levels, following first-order kinetics, with relatively long half-lives, suggesting potential for absorption into circulation without significant degradation.
ACS Omega. 2023 Oct;8(42):39490-39510.
PMID: 37901542 [PubMed - as supplied by publisher]
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| 2. |
Guided discovery of hepatoprotective polyhydroxy cembrane-type diterpenoids from the gum resin of Boswellia carterii by MS/MS molecular networking.
Yu J, Zhao L, Wang Z, Yue T, Wang X
Seven previously undescribed polyhydroxy cembrane-type diterpenoids, olibanols A-G (1-7) were obtained from the gum resin of Boswellia carterii by means of MS/MS molecular networking. Compound 2 possessed four hydroxy groups, 1, 3, 4, 5, and 6 had three hydroxy groups, 7 with one hydroxy group, among which 1 and 4 were a pair of epimers with double bond at C-3 and hydroxy at C-8. Structures of these previously undescribed compounds were determined by NMR analysis and ECD calculations. All the polyhydroxy cembrane-type diterpenoids obtained were assayed for their hepatoprotective effects against the anti-tuberculosis drug-induced hepatic damage to the HRZ-induced HepG2 cells. As results indicated, compounds 3, 4, and 6 showed significant hepatoprotective effects against the hepatic damage via the Nrf2 signal pathway, which could be developed as potential hepatoprotective agents against the anti-tuberculosis drug-induced hepatic damage.
Phytochemistry. 2023 Dec;216():113897.
PMID: 37866446 [PubMed - indexed for MEDLINE]
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| 3. |
Pathophysiology of diabetic hepatopathy and molecular mechanisms underlying the hepatoprotective effects of phytochemicals.
Mobasheri L, Ahadi M, Beheshti Namdar A, Alavi MS, Bemidinezhad A, Moshirian Farahi SM, Esmaeilizadeh M, Nikpasand N, Einafshar E, Ghorbani A
Patients with diabetes are at risk for liver disorders including glycogen hepatopathy, non-alcoholic fatty liver disease, cirrhosis, and hepatic fibrosis. The pathophysiological mechanisms behind diabetic hepatopathy are complex, some of them include fatty acid accumulation, increased reactive oxygen species, increased advanced glycation end-products, hyperactivity of polyol pathways, increased apoptosis and necrosis, and promotion of fibrosis. A growing number of studies have shown that herbal extracts and their active phytochemicals have antihyperglycemic properties and beneficial effects on diabetic complications. The current review, for the first time, focused on herbal agents that showed beneficial effects on diabetic hepatopathy. For example, animal studies have shown that Moringa oleifera and Morus alba improve liver function in both type-1 and type-2 diabetes. Also, evidence from clinical trials suggests that Boswellia serrata, Juglans regia, Melissa officinalis, Portulaca oleracea, Silybum marianum, Talapotaka Churna, and Urtica dioica reduce serum liver enzymes in diabetic patients. The main active ingredient of these plants to protect the liver seems to be phenolic compounds such as niazirin, chlorogenic acid, resveratrol, etc. Mechanisms responsible for the hepatoprotective activity of herbal agents include improving glucose metabolism, restoring adipokines levels, antioxidant defense, and anti-inflammatory activity. Several signaling pathways are involved in hepatoprotective effects of herbal agents in diabetes, such as phosphoinositide 3-kinase, adenosine monophosphate-activated protein kinase, mitogen-activated protein kinase, and c-Jun NH2-terminal kinase.
Biomed Pharmacother. 2023 Nov;167():115502.
PMID: 37734266 [PubMed - as supplied by publisher]
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| 4. |
Regulation of NOX/p38 MAPK/PPARα pathways and miR-155 expression by boswellic acids reduces hepatic injury in experimentally-induced alcoholic liver disease mouse model: novel mechanistic insight.
Salama RM, Abbas SS, Darwish SF, Sallam AA, Elmongy NF, El Wakeel SA
Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in Boswellia serrata, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.
Arch Pharm Res. 2023 Apr;46(4):323-338.
PMID: 36959348 [PubMed - indexed for MEDLINE]
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| 5. |
Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways.
Zheng P, Huang Z, Tong DC, Zhou Q, Tian S, Chen BW, Ning DM, Guo YM, Zhu WH, Long Y, Xiao W, Deng Z, Lei YC, Tian XF
BACKGROUND: In traditional Chinese medicine (TCM), frankincense and myrrh are the main components of the antitumor drug Xihuang Pill. These compounds show anticancer activity in other biological systems. However, whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma (HCC) is unknown, and the potential molecular mechanism(s) has not yet been determined.
AIM: To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh .
METHODS: In the present study, which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (http://tcmspw.com/tcmsp.php), Universal Protein database (http://www.uniprot.org), GeneCards: The Human Gene Database (http://www.genecards.org/) and Comparative Toxicogenomics Database (http://www.ctdbase.org/), the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted. The core prediction targets were screened by molecular docking. , SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model, and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d. The tumors were collected and evaluated: the tumor volume and growth rate were gauged to evaluate tumor growth; hematoxylin-eosin staining was performed to estimate histopathological changes; immunofluorescence (IF) was performed to detect the expression of CD31, α-SMA and collagen IV; transmission electron microscopy (TEM) was conducted to observe the morphological structure of vascular cells; enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of secreted HIF-1α and TNF-α; reverse transcription-polymerase chain reaction (RT-qPCR) was performed to measure the mRNA expression of HIF-1α, TNF-α, VEGF and MMP-9; and Western blot (WB) was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.
RESULTS: The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets. The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets, with the greatest affinity for EGFR. Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes, such as cytokine-receptor binding, and pathways, such as those involving serine/threonine protein kinase complexes and MAPK, HIF-1 and ErbB signaling cascades. The animal experiment results were verified. First, we found that, through frankincense and/or myrrh treatment, the volume of subcutaneously transplanted HCC tumors was significantly reduced, and the pathological morphology was attenuated. Then, IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression, increased the coverage of perivascular cells, tightened the connection between cells, and improved the shape of blood vessels. In addition, ELISA, RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors, inflammatory factors and angiogenesis-related factors, namely, HIF-1α, TNF-α, VEGF and MMP-9. Furthermore, mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation, thereby inhibiting the phosphorylation activity of its downstream targets: the PI3K/Akt and MAPK (ERK, p38 and JNK) pathways.
CONCLUSION: In summary, frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects EGFR-activated PI3K/Akt and MAPK signaling pathways, highlighting the potential of this dual TCM compound as an anti-HCC candidate.
World J Gastrointest Oncol. 2022 Feb;14(2):450-477.
PMID: 35317323 [PubMed - as supplied by publisher]
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| 6. |
Anti-inflammatory and hepatoprotective cembranoid alcohols from the Gum Resin of Boswellia carterii.
Yu J, Zhao L, Zhang K, Wang X
Five undescribed cembranoid alcohols, boscartinols A-E (1-5) were discovered from the gum resin of Boswellia carterii. Their structures were elucidated by analyzing the spectroscopic data. Notably, all these five compounds preserved an isopropyl type cembranoid skeleton, featured the same groups of one epoxy ring at C-C and one hydroxy group at C-11, as well as two double bonds migrating from C to C and one hydroxy group from C to C within the cembranoid structure. These cembranoids were evaluated for the hepatoprotective and anti-inflammatory activities using two cell models of APAP-induced HepG2 and LPS-induced RAW 264.7. For hepatoprotective activity, compounds 1 and 5 showed remarkable hepatoprotective activity (inhibition rate of 51.6% and 39.8%, respectively) at 10 μM, with the other three compounds of 2-4 showing less potently hepatoprotective. For anti-inflammatory activity, compounds 2-4 showed significant inhibitory effects on NO produced by LPS-induced RAW 264.7 cell (IC values of 13.40 μM, 7.08 μM and 14.26 μM), with the other two compounds of 1 and 5 showing less potently anti-inflammatory activities.
Fitoterapia. 2021 Nov;155():105064.
PMID: 34656670 [PubMed - indexed for MEDLINE]
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| 7. |
Evaluation of the solubility of 11-keto-β-boswellic acid and its histological effect on the diabetic mice liver using a novel technique.
Amri IA, Mabood F, Kadim IT, Alkindi A, Al-Harrasi A, Al-Hashmi S, Abbas G, Hamaed A, Ahmed B, Al-Shuhaimi J, Khalaf S, Shaikh J
BACKGROUND AND AIM: The literature is scant on the effect of 11-keto-β-boswellic acid (KBA) on the liver of diabetes-induced mice. This study was designed to develop a rapid, sensitive, accurate, and inexpensive detection technique for evaluating the solubility of KBA obtained from the gum resin of Omani frankincense () in the liver of streptozotocin-induced diabetic mice using Fourier transform infrared (FTIR) reflectance spectroscopy coupled with principal components analysis (PCA). It also aimed to investigate the effect of KBA on histological changes in the hepatocytes of diabetic mice.
MATERIALS AND METHODS: Eighteen mice were assigned to the healthy control group, the diabetic control group, or the KBA-treated diabetic group. Liver tissue samples from all groups were scanned using an FTIR reflectance spectrophotometer in reflection mode. FTIR reflectance spectra were collected in the wavenumber range of 400-4000 cm using an attenuated total reflectance apparatus.
RESULTS: FTIR reflectance spectra were analyzed using PCA. The PCA score plot, which is an exploratory multivariate data set, revealed complete segregation among the three groups' liver samples based on changes in the variation of wavenumber position in the FTIR reflectance spectra, which indicated a clear effect of KBA solubility on treatments. Histological analysis showed an improvement in the liver tissues, with normal structures of hepatocytes exhibiting mild vacuolation in their cytoplasm.
CONCLUSION: KBA improved the morphology of liver tissues in the diabetic mice and led to complete recovery of the damage observed in the diabetic control group. FTIR reflectance spectroscopy coupled with PCA could be deployed as a rapid, low-cost, and non-destructive detection method for evaluating treatment effects in diseased liver tissue based on the solubility of KBA.
Vet World. 2021 Jul;14(7):1797-1803.
PMID: 34475700 [PubMed - as supplied by publisher]
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| 8. |
Boswellia Serrata
Boswellia also called Indian Frankincense is an extract of the gummy oleoresin derived from beneath the bark of the Boswellia serrata tree, which is native to India, the Middle East and Northern Africa. The resin is rich in triterpenic acids and has been used for centuries in traditional Ayurvedic medicine to treat inflammatory conditions. More recently, Boswellia serrata extracts have been marketed as helpful in arthritis, colitis and asthma. Extracts of Boswellia serrata have not been linked to serum aminotransferase elevations during treatment or to instances of clinically apparent acute liver injury.
. 2012;():.
PMID: 33151656 [PubMed - as supplied by publisher]
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| 9. |
Bioactive cembrane diterpenoids from the gum resin of Boswellia carterii.
Yu J, Zhao L, Sun X, Geng Y, Wang X
Eight new cembrane-type diterpenoids, boscartins AP-AW (1-8) were obtained from the gum resin of Boswellia carterii. Among which, six ones (2-7) were isomers, with one hydroxy group and two double bonds migrating along the carbocycle. The structures were elucidated by spectroscopic examination. All isolates were evaluated for anti-inflammatory activity and hepatoprotective activity by cell models of LPS-induced RAW 264.7 mouse peritoneal macrophages and APAP-induced HepG2 cells, respectively. As for anti-inflammatory activity assay, compound 1 exhibited potent activity against NO production (IC of 13.1 μM), with the other ones exhibiting weak anti-inflammatory activity (IC > 50 μM). As for hepatoprotective activity assay, compound 1 exhibited more significant activity (inhibition rate of 30.7%) than that of the positive control (bicyclol, inhibition rate of 27.2%), and compounds 4, and 6 showed nearly the same activities as the control (inhibition rates of 26.7% and 25.9%, respectively), with the other ones exhibiting weak hepatoprotective activity.
Fitoterapia. 2020 Oct;146():104699.
PMID: 32763364 [PubMed - indexed for MEDLINE]
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| 10. |
Ten undescribed cembrane-type diterpenoids from the gum resin of Boswellia sacra and their biological activities.
Wang JJ, Sun HR, Suo XY, Xue Wang , Sun H, Wang XL, Jiang JD, Ji TF
Ten undescribed cembrane-type diterpenes boscartins AL-AU, as well as five known analogues were isolated from Boswellia sacra Flueck. The relative configurations of these boscartins were established by extensive spectroscopic analysis of NMR spectra, IR and MS. The absolute configurations of boscartin AL, boscartin AN and isoincensole oxide were unequivocally assigned by single crystal X-ray diffraction. Meanwhile, the absolute configurations of boscartin AM, boscartin AP and boscartin AQ were determined by an empirical in situ formed Rh-complex ECD method. Biological evaluations showed that four compounds exhibited obvious hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 μM. Regarding neuroprotective activity, some isolates displayed moderate to evident protective effects against glutamate-induced toxicity in primary cultured fetal rat cortical neurons or oxygen-glucose deprivation toxicity in SK-N-SH Cells at 10 μM.
Phytochemistry. 2020 Sep;177():112425.
PMID: 32535347 [PubMed - indexed for MEDLINE]
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| 11. |
Boswellic acid protects against Bisphenol-A and gamma radiation induced hepatic steatosis and cardiac remodelling in rats: role of hepatic PPAR-α/P38 and cardiac Calcineurin-A/NFATc1/P38 pathways.
Thabet NM, Abdel-Rafei MK, Moustafa EM
Bisphenol-A (BPA) and gamma-radiation are two risky environmental pollutants that human beings are exposed to in everyday life and consequently they threaten human health via inducing oxidative stress, inflammation, and eventually tissue damage. This study aims at appraising the protective effect of Boswellic Acid (BA) (250 mg/kg/day, orally) administration on BPA (150 mg/kg/day, i.p) and γ-irradiation (IR) (3 Gy/week for 4 weeks up to cumulative dose of 12 Gy/experimental course) for 4 weeks-induced damage to liver and heart tissues of rats. The present results indicated a significant improvement against damage induced by BPA and IR revealed in biochemical investigations (hepatic PPAR-α/P38 and cardiac ET-1/Calcineurin-A/NFATc1/P38) and histopathological examination of liver and heart. It could be concluded that BA possesses a protective effect against these two deleterious environmental pollutants which attracted major global concerns due to their serious toxicological impact on human health.
Arch Physiol Biochem. 2022 Jun;128(3):767-785.
PMID: 32057248 [PubMed - indexed for MEDLINE]
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| 12. |
Antioxidant, anti-inflammatory and anti-fibrotic effects of gum resin in CCl-induced hepatotoxicity.
Eltahir HM, Fawzy MA, Mohamed EM, Alrehany MA, Shehata AM, Abouzied MM
The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl-induced liver fibrosis; group III, CCl-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl-induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-β, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics.
Exp Ther Med. 2020 Feb;19(2):1313-1321.
PMID: 32010304 [PubMed - as supplied by publisher]
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| 13. |
Cembrane-type diterpenoids from the gum resin of and their biological activities.
Sun X, Geng Y, Wang X, Qin D, Yu J
Eight new cembrane-type diterpenoids, boscartins AH-AK (1-8), along with two known ones (9-10), were isolated from the gum resin of . Compounds 1-3 were characteristic of high oxidation assignable to three epoxy groups, while compounds 4-8 were characteristic of two epoxy groups. Spectroscopic examination was used to elucidate their structures. All isolates were evaluated for antiproliferative activity against HCT-116 human colon cancer cells, anti-inflammatory activity against nitric oxide (NO) production, and hepatoprotective activity . All of them showed weak antiproliferative activity (IC > 100 μM), 8 exhibited potent inhibitory effects on NO production (IC of 14.8 μM), with the others showing weak anti-inflammatory activity (IC > 30 μM), and 1 exhibited more potent hepatoprotective activity than the positive control, bicyclol, at 10 μM against the damage induced by paracetamol in HepG2 cells.
RSC Adv. 2020 Jan;10(2):746-755.
PMID: 35494443 [PubMed - as supplied by publisher]
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| 14. |
Bioactive cembrane-type diterpenoids from the gum-resin of Boswellia carterii.
Wang YG, Ren J, Ma J, Yang JB, Ji T, Wang AG
Chemical examination of the gum-resin of Boswellia carterii resulted in the isolation and characterization of eighteen new cembrane-type diterpenoids, named as Boscartins P-AG (1-18) and eight known ones. Their structures were established on the basis of extensive spectroscopic (2D NMR, IR, CD, MS and X-ray) analysis in combination with modified Mosher's method. All compounds featured unusual 1,12-oxygenated tetrahydrofuran functionalities, and were evaluated for hepatoprotective activity against D-galactosamine-induced HL-7702 cell damage and cytotoxic activity against MCF-7 human breast cancer cell in vitro. Compounds 1, 6-10, 12-13, 16-17 and 21-25 (10 μM) showed some hepatoprotective activity against D-galactosamine-induced HL-7702 cell damage.
Fitoterapia. 2019 Sep;137():104263.
PMID: 31295512 [PubMed - indexed for MEDLINE]
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| 15. |
Acetyl-11-keto-β-boswellic acid triggers premature senescence via induction of DNA damage accompanied by impairment of DNA repair genes in hepatocellular carcinoma cells in vitro and in vivo.
Wang S, Wang H, Sun B, Li D, Wu J, Li J, Tian X, Qin C, Chang H, Liu Y
Cellular senescence, a state of irreversible growth arrest, occurs in all somatic cells and causes the cells to exhaust replicative capacity. Recently, cellular senescence has been emerging as one of the principal mechanisms of tumor suppression, which can be induced by low doses of therapeutic drugs in cancer cells. Acetyl-11-keto-β-boswellic acid (AKBA), an active ingredient isolated from the plant Boswellia serrata, has been identified to induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we found that low concentrations of AKBA treatment triggered cell growth arrest at G0/G1 phase with features of premature cellular senescence phenotype in both HCC cell lines HepG2 and SMMC7721, as observed by enlarged and flattened morphology, significant increase in cells with senescence-associated β-galactosidase staining, and decrease in cell proliferation and DNA synthesis. Furthermore, cellular senescence induced by AKBA occurred via activation of DNA damage response and impairment of DNA repair, as evidenced by strong induction of γH2AX and p53, and downregulated expressions of multiple DNA repair associated genes. Induction of p53 by AKBA caused a significant increase in p21 , which had a critical involvement in the induction of cellular senescence. Additionally, in vivo study demonstrated that induction of senescence contributed to the anticancer efficacy of AKBA. Therefore, our findings suggested that induction of premature senescence by AKBA through DNA damage response accompanied by impairment of DNA repair genes defines a novel mechanism contributing to its growth suppression in HCC cells.
Fundam Clin Pharmacol. 2020 Feb;34(1):65-76.
PMID: 31141202 [PubMed - indexed for MEDLINE]
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| 16. |
Boscartins L-O: Cembrane-type diterpenoids from the gum resin of Boswellia sacra Flueck.
Wang J, Zhen B, Hu J, Shi M, Wei C, Wang X, Sun H, Ji T
Four undescribed cembrane-type diterpenoids, boscartins L-O, as well as five known compounds (1S, 3R, 11S, 12R, 7E)-1,12-epoxy-4-methylenecembr-7- ene- 3,11-diol, isoincensole oxide, incensole oxide, incensole acetate and incensole oxide acetate were isolated from the gum resin of Boswellia sacra Flueck. (Burseraceae). The structures of these compounds were elucidated by extensive 1D and 2D NMR spectroscopic and mass spectrometric analysis, as well as comparisons with known compounds. The absolute configurations of the known compound (1S, 3R, 7E, 11S, 12R)-1,12-epoxy-4-methylenecembr-7-ene-3,11-diol was unequivocally confirmed by single-crystal X-ray diffraction analysis with Cu Kα radiation. Incensole acetate exhibited significant hepatoprotective activity at 10 μM against paracetamol-induced HepG2 cell damage.
Phytochemistry. 2019 Jul;163():126-131.
PMID: 31059964 [PubMed - indexed for MEDLINE]
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| 17. |
An Approach to Treatment of Liver Cancer by Novel Glycyrrhizin Derivative.
El-Senduny FF, Zidane MM, Youssef MM, Badria FA
BACKGROUND: Liver cancer is a life threating disease as it is the fifth most common cancer and the third most common cause of death worldwide with no safe, efficient, and economic drug available for treatment.
METHODS: This study intended to investigate glycyrrhizin and its derivatives for possible use as a cytotoxic agent and as a drug for liver cancer treatment. Thus, after treatment of liver cancer cell line HepG-2 with 50 μM of each compound, cell viability was determined.
RESULTS: The cytotoxicity assay showed glycyrrhizin derivatives ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-acetyl-11- keto-β-Boswellic acid) to be the most potent drug against liver cancer cell line HepG-2 with IC50 values 25.50 ± 1.06 and 19.73 ± 0.89 μM, respectively. Both the compounds showed higher selectivity towards hepatocellular carcinoma rather than the normal lung fibroblast cell line WI-38. The presence of methyl ester at C-30 greatly increased the cytotoxicity of ME-GA which might be attributed to its higher activity and selectivity. Both ME-GA and AKBA contributed to inhibit cancer cell migration in the wound healing assay and impeded colony formation. The use of flow cytometry to carry out cell cycle analysis and the determination of possible mechanisms of action for apoptosis revealed that ME-GA arrested the cell cycle at G2/M that led to the inhibition of hepatocellular carcinoma and induced apoptosis via the extrinsic pathway and its ability to increase p53 transactivation.
CONCLUSION: This work highlights the cytotoxicity of glycyrrhizin and its derivatives for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. The most cytotoxic compound was ME-GA (18β-Glycyrrhetinic-30-methyl ester) with no cytotoxic effect on the normal cell line. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer.
Anticancer Agents Med Chem. 2019;19(15):1863-1873.
PMID: 30973113 [PubMed - indexed for MEDLINE]
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| 18. |
Protective Effect of Boswellic Acids against Doxorubicin-Induced Hepatotoxicity: Impact on Nrf2/HO-1 Defense Pathway.
Barakat BM, Ahmed HI, Bahr HI, Elbahaie AM
The current study aimed to investigate the potential protective role of boswellic acids (BAs) against doxorubicin- (DOX-) induced hepatotoxicity. Also, the possible mechanisms underlying this protection; antioxidant, as well as the modulatory effect on the Nrf2 transcription factor/hem oxygenase-1 (Nrf2/HO-1) pathway in liver tissues, was investigated. Animals were allocated to five groups: group 1: the saline control, group 2: the DOX group, animals received DOX (6 mg/kg, i.p.) weekly for a period of three weeks, and groups 3-5: animals received DOX (6 mg/kg, i.p.) weekly and received protective doses of BAs (125, 250, and 500 mg/kg/day). Treatment with BAs significantly improved the altered liver enzyme activities and oxidative stress markers. This was coupled with significant improvement in liver histopathological features. BAs increased the Nrf2 and HO-1 expression, which provided protection against DOX-induced oxidative insult. The present results demonstrated that BAs appear to scavenge ROS and inhibit lipid peroxidation and DNA damage of DOX-induced hepatotoxicity. The antioxidant efficacy of BAs might arise from its modulation of the Nrf2/HO-1 pathway and thereby protected liver from DOX-induced oxidative injury.
Oxid Med Cell Longev. 2018;2018():8296451.
PMID: 29541348 [PubMed - indexed for MEDLINE]
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| 19. |
Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Corrected and republished from: Biomedicine (Taipei). 2016 Jun; 6 (2): 9. doi: 10.7603/s40681-016-0009-1PMCID: PMC4864770.
Chen LC, Hu LH, Yin MC
Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver. BA intake at both doses alleviated subsequent APAP-induced oxidative stress by retaining GSH content, decreasing ROS and GSSG formations, reserving activity and expression of GR and HO-1 in liver, and lowering hepatic cytochrome P450 2E1 activity and expression. APAP treatment enhanced hepatic levels of interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1. BA pre-intake diminished APAP-induced release of those inflammatory cytokines and chemokines. APAP up-regulated hepatic protein expression of toll-like receptor (TLR)-3, TLR-4, MyD88, nuclear factor kappa B (NF-κB) p50, NF-κB p65 and JNK. BA pre-intake at both doses suppressed the expression of NF-κB p65 and p-JNK, and only at 0.1% down-regulated hepatic TLR-3, TLR-4 and MyD88 expression. APAP led to obvious foci of inflammatory cell infiltration in liver, determined by H&E stain. BA intake at both doses attenuated hepatic inflammatory infiltration. These findings support that boswellic acid is a potent hepato-protective agent.
Biomedicine (Taipei). 2017 Jun;7(2):13.
PMID: 28612711 [PubMed - as supplied by publisher]
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| 20. |
Correction notice to: Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Biomedicine (Taipei). 2016 Jun; 6 (2): 9. DOI: 10.7603/s40681-016-0009-1.
Chen LC, Hu LH, Yin MC
Biomedicine (Taipei). 2017 Mar;7(1):7.
PMID: 28474583 [PubMed - as supplied by publisher]
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| 21. |
Understanding the role of 3-O-Acetyl-11-keto-β-boswellic acid in conditions of oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.
Kumar M, Singh G, Bhardwaj P, Dhatwalia SK, Dhawan DK
The present study was planned to see whether 3-O-Acetyl-11- keto-β-boswellic acid has any protective effects against benzo(a)pyrene (BaP) induced toxicity or not. In vitro studies show concentration dependent linear association of radical scavenging activity of AK which is comparable to ascorbic acid taken as reference compound. For in vivo studies, the animals were divided randomly into five groups which included a) normal control, b) vehicle treated (olive oil), c) BaP treated, d) AK treated and e) AK + BaP (combined treated). BaP was administered at a dose of 50mg/kg in olive oil twice a week orally for 4 weeks and AK (50mg/kg) was given in olive oil thrice a week for 4 weeks before and after BaP exposure. BaP treated animals showed a significant increase (p < 0.001) in lipid peroxidation (LPO) and protein carbonyl contents (PCC) in hepatic tissue. Further, a significant increase (p < 0.001) in the liver marker enzymes as well as citrulline and nitric oxide levels in the hepatic tissue was also observed. Interestingly, AK when supplemented to BaP treated animals ameliorated the above said biochemical indices appreciately. The histopathological observations also showed appreciable improvement when BaP treated animals were supplemented with AK, thus emphasing the protective potential of AK.
Food Chem Toxicol. 2017 Nov;109(Pt 2):871-878.
PMID: 28363852 [PubMed - indexed for MEDLINE]
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| 22. |
Effect of Boswellia serrata Resin Supplementation on Basic Chemical and Mineral Element Composition in the Muscles and Liver of Broiler Chickens.
Al-Yasiry ARM, Kiczorowska B, Samolińska W
Supplementation of broiler chicken diets with resin rich in bioactive components, such as different boswellic acids, could improve productivity, chemical composition, and nutritive value of produced meat. The aim of the study was to assess the effect of different levels of Boswellia serrata (BSR) supplementation in broiler chicken diet on the basic chemical composition and the Ca, P, Mg, Fe, Zn, and Cu contents in the breast and drumstick muscles and liver. The analyses involved 200 Ross 308 chickens. The broiler chickens were fed with diets containing 0 (BSR0), 1.5 (BSR1.5), 2 (BSR2), and 2.5% (BSR2.5) of B. serrata resin. The supplementation of broiler chicken diets with 2.5% (BSR2.5) decreased linearly the ether extract in breast and drumstick muscles and the calorific value in drumstick muscles (P < 0.05). An increased level of Ca in the breast and drumstick muscles (control vs. BSR diets, linear, P < 0.05) and in the liver (control vs. BSR diets, quadratic, P < 0.05) as well as Mg in the drumstick muscles and liver (control vs. BSR diets, linear, P < 0.05) was noted in the BSR2 and BSR2.5 chicken groups. The BSR supplementation reduced Cu (in the breast and drumstick muscles and liver) (P < 0.05) and Zn retention (in the drumstick muscles) (C vs. BSR, linear, P < 0.05). B. serrata resin can be considered a good feed additive with a positive impact on the dietary value of poultry meat.
Biol Trace Elem Res. 2017 Oct;179(2):294-303.
PMID: 28210929 [PubMed - indexed for MEDLINE]
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| 23. |
Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury.
Chen LC, Hu LH, Yin MC
Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver. BA intake at both doses alleviated subsequent APAP-induced oxidative stress by retaining GSH content, decreasing ROS and GSSG formations, reserving activity and expression of GR and HO-1 in liver, and lowering hepatic cytochrome P450 2E1 activity and expression. APAP treatment enhanced hepatic levels of interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1. BA pre-intake diminished APAP-induced release of those inflammatory cytokines and chemokines. APAP upregulated hepatic protein expression of toll-like receptor (TLR)-3, TLR-4, MyD88, nuclear factor kappa B (NF-κB) p50, NF-κB p65 and JNK. BA pre-intake at both doses suppressed the expression of NF-κB p65 and p-JNK, and only at 0.1% down-regulated hepatic TLR-3, TLR-4 and MyD88 expression. APAP led to obvious foci of inflammatory cell infiltration in liver, determined by H&E stain. BA intake at both doses attenuated hepatic inflammatory infiltration. These findings support that boswellic acid is a potent hepatoprotective agent.
Biomedicine (Taipei). 2016 Jun;6(2):9.
PMID: 27161000 [PubMed - as supplied by publisher]
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| 24. |
Hepatoprotective triterpenes from the gum resin of Boswellia carterii.
Wang YG, Ma QG, Tian J, Ren J, Wang AG, Ji TF, Yang JB, Su YL
Ten tirucallane-type triterpenes named boscartene A-J and a nor-tetracyclic triterpene boscartene K, together with ten known compounds were isolated from the gum resin of Boswellia carterii Birdw. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis. In vitro assay, some of these compounds (10 μM) showed moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage.
Fitoterapia. 2016 Mar;109():266-73.
PMID: 26739386 [PubMed - indexed for MEDLINE]
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| 25. |
Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure.
Zaitone SA, Barakat BM, Bilasy SE, Fawzy MS, Abdelaziz EZ, Farag NE
Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance, oxidative stress, and cytokine imbalance. Boswellic acids, a series of pentacyclic triterpene molecules that are produced by plants in the genus Boswellia, has been traditionally used for the treatment of a variety of diseases. This study aimed at evaluating the protective effect of boswellic acids in a model of diet-induced NAFLD in rats in comparison to the standard insulin sensitizer, pioglitazone. Rats were fed with a high-fat diet (HFD) for 12 weeks to induce NAFLD. Starting from week 5, rats received boswellic acids (125 or 250 mg/kg) or pioglitazone parallel to the HFD. Feeding with HFD induced hepatic steatosis and inflammation in rats. In addition, liver index, insulin resistance index, activities of liver enzymes, and serum lipids deviated from normal. Further, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase 2 were elevated; this was associated with an increase in hepatic expression of inducible nitric oxide synthase (iNOS) and formation of 4-hydroxy-2-nonenal (HNE). Rats treated with boswellic acids (125 or 250 mg/kg) or pioglitazone showed improved insulin sensitivity and a reduction in liver index, activities of liver enzymes, serum TNF-α and IL-6 as well as hepatic iNOS expression and HNE formation compared to HFD group. Furthermore, at the cellular level, boswellic acids (250 mg/kg) ameliorated the expression of thermogenesis-related mitochondrial uncoupling protein-1 and carnitine palmitoyl transferase-1 in white adipose tissues. Data from this study indicated that boswellic acids might be a promising therapy in the clinical management of NAFLD if appropriate safety and efficacy data are available.
Naunyn Schmiedebergs Arch Pharmacol. 2015 Jun;388(6):587-600.
PMID: 25708949 [PubMed - indexed for MEDLINE]
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| 26. |
Antioxidant and hepatoprotective effects of Boswellia ovalifoliolata bark extracts.
Mahesh BU, Shrivastava S, Pragada RR, Naidu VG, Sistla R
Paracetamol (PCM) hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata (BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.
Chin J Nat Med. 2014 Sep;12(9):663-71.
PMID: 25263977 [PubMed - indexed for MEDLINE]
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| 27. |
Caspase mediated synergistic effect of Boswellia serrata extract in combination with doxorubicin against human hepatocellular carcinoma.
Khan MA, Singh M, Khan MS, Najmi AK, Ahmad S
The study investigated the growth-inhibiting and apoptosis mediating effects of B. serrata extract as monotherapy and combination therapy with DOX against hepatocellular carcinoma cell lines. Boswellic acid rich fraction of B. serrata extract was prepared. MTT assay on HepG2 and Hep3B cells was carried out using B. serrata alone and in combination with DOX. Further, caspase-3 activity, TNF-α level, and IL-6 level were estimated. Isobolographic analysis was carried out to evaluate the effect of combination therapy. Additionally, protective effect of B. serrata extract on DOX induced hepatic toxicity was also evaluated in Wistar rats. B. serrata extract inhibited growth of HepG2 (IC50 value of 21.21 ± 0.92 μg/mL) as well as HepG2 (IC50 value of 18.65 ± 0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of 1.06 ± 0.04 μg/mL and 1.92 ± 0.09 μg/mL. Isobolographic analysis showed combination index (CI) of DOX and B. serrata extract of 0.53 ± 0.03 to 0.79 ± 0.02 suggesting synergistic behavior against the two cell lines. B. serrata extract also caused dose dependent increase in caspase-3 activity, TNF-α level, and IL-6 level which was higher (P < 0.001) with DOX (1 μM) and B. serrata extract (20 μg/mL) combination. B. serrata extract also protected Wistar rats against DOX induced hepatic toxicity.
Biomed Res Int. 2014;2014():294143.
PMID: 25177685 [PubMed - indexed for MEDLINE]
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| 28. |
A boswellic acid-containing extract ameliorates schistosomiasis liver granuloma and fibrosis through regulating NF-κB signaling in mice.
Liu M, Wu Q, Chen P, Büchele B, Bian M, Dong S, Huang D, Ren C, Zhang Y, Hou X, Simmet T, Shen J
Boswellic acid (BA)-containing extracts such as BSE have anti-inflammatory and immunomodulatory activity. In chronic schistosomiasis, the hepatic granuloma and fibrosis induced by egg deposition in the liver is the most serious pathological manifestations. However, little is known regarding the role of BAs in Schistosoma japonicum (S. japonicum) egg-induced liver granuloma and fibrosis. In order to investigate the effect of a water-soluble complex preparation of BSE, BSE-CD, on S. japonicum egg-induced liver pathology, liver granuloma and fibrosis were induced by infecting C57BL/6 mice with 18-22 cercariae of S. japonicum. S. japonicum cercariae infected mice were injected with BSE-CD at the onset of egg granuloma formation (early phase BSE-CD treatment after 4 weeks infection) or after the formation of liver fibrosis (late phase BSE-CD treatment after 7 weeks infection). Our data show that treatment of infected mice with BSE-CD significantly reduced both the extent of hepatic granuloma and fibrosis. Consistent with an inhibition of NF-κB signaling as evidenced by reduced IκB kinase (IKK) activation, the mRNA expression of VEGF (vascular endothelial growth factor, VEGF), TNF-α (tumor necrosis factor-alpha TNF-α) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover, immunohistochemical analysis (IHC) revealed that the content of α-SMA in liver tissue of BSE-CD treated mice was dramatically decreased. Our findings suggest that BSE-CD treatment attenuates S. japonicum egg-induced hepatic granulomas and fibrosis, at least partly due to reduced NF-κB signaling and the subsequently decreased expression of VEGF, TNF-α, and MCP-1. Suppression of the activation of hepatic stellate cells (HSC) may also be involved in the therapeutic efficacy of BSE-CD.
PLoS One. 2014;9(6):e100129.
PMID: 24941000 [PubMed - indexed for MEDLINE]
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| 29. |
Ultrastructural and hormonal changes in rat cauda epididymal spermatozoa induced by Boswellia papyrifera and Boswellia carterii.
Ahmed M, Ali D, Harrath AH, Hussain T, Al-Daghri N, Alokail MS, Aladakatti RH, Ghodesawar MA
Boswellia papyrifera and Boswellia carterii diffuses smoke polluting air that adversely affects indoor environment that certainly harm human health. Therefore, this study aims at ascertaining the effect of these plants on gonadal hormones and molecular changes in rat spermatozoa. The animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily for 120 days along with suitable controls. Significant decreases in FSH, LH and testosterone levels were evidenced, along with a reduction of protein, sialic acid, and carnitine levels. In sperm physiology, sperm count, motility, speed decrease, whereas sperm anomalies increase. TEM observation indicates morphological changes in plasma and acrosomal membranes, cytoplasmic droplet in the tail region, vacuolated, and disorganization of the mitochondrial sheath. These findings demonstrate that B. papyrifera and B. carterii smoke affects the process of sperm formation and maturation, which indicates the detrimental effects of these plants on the reproductive system.
C R Biol. 2014 Apr;337(4):250-7.
PMID: 24702894 [PubMed - indexed for MEDLINE]
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| 30. |
Hepatoprotective prenylaromadendrane-type diterpenes from the gum resin of Boswellia carterii.
Wang YG, Ren J, Wang AG, Yang JB, Ji TF, Ma QG, Tian J, Su YL
Chemical examination of the exuded gum resin of Boswellia carterii resulted in the isolation of nine new prenylaromadendrane-type diterpenes, boscartols A-I (1-9). The structures of these compounds were established by extensive 1D and 2D NMR spectroscopic analyses, mass spectrometric data, and circular dichroism spectra. Compounds 1-3, 5, 6, 8, and 9 (10 μM) showed moderate hepatoprotective activity against d-galactosamine-induced HL-7702 cell damage.
J Nat Prod. 2013 Nov;76(11):2074-9.
PMID: 24195447 [PubMed - indexed for MEDLINE]
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| 31. |
The tyrosine phosphatase SHP-1 inhibits proliferation of activated hepatic stellate cells by impairing PDGF receptor signaling.
Tibaldi E, Zonta F, Bordin L, Magrin E, Gringeri E, Cillo U, Idotta G, Pagano MA, Brunati AM
The dimerization and auto-transphosphorylation of platelet-derived growth factor receptor (PDGFR) upon engagement by platelet-derived growth factor (PDGF) activates signals promoting the mitogenic response of hepatic stellate cells (HSCs) due to liver injury, thus contributing to the development of hepatic fibrosis. We demonstrate that the tyrosine phosphatases Src homology 2 domain-containing phosphatase 1 and 2 (SHP-1 and SHP-2) act as crucial regulators of a complex signaling network orchestrated by PDGFR activation in a spatio-temporal manner with diverse and opposing functions in HSCs. In fact, silencing of either phosphatase shows that SHP-2 is committed to PDGFR-mediated cell proliferation, whereas SHP-1 dephosphorylates PDGFR hence abrogating the downstream signaling pathways that result in HSC activation. In this regard, SHP-1 as an off-switch of PDGFR signaling appears to emerge as a valuable molecular target to trigger as to prevent HSC proliferation and the fibrogenic effects of HSC activation. We show that boswellic acid, a multitarget compound with potent anti-inflammatory action, exerts an anti-proliferative effect on HSCs, as in other cell models, by upregulating SHP-1 with subsequent dephosphorylation of PDGFR-β and downregulation of PDGF-dependent signaling after PDGF stimulation. Moreover, the synergism resulting from the combined use of boswellic acid and imatinib, which directly inhibits PDGFR-β activity, on activated HSCs offers new perspectives for the development of therapeutic strategies that could implement molecules affecting diverse players of this molecular circuit, thus paving the way to multi-drug low-dose regimens for liver fibrosis.
Biochim Biophys Acta. 2014 Feb;1843(2):288-98.
PMID: 24140598 [PubMed - indexed for MEDLINE]
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| 32. |
A boswellic acid-containing extract attenuates hepatic granuloma in C57BL/6 mice infected with Schistosoma japonicum.
Liu M, Chen P, Büchele B, Dong S, Huang D, Ren C, Zhang Y, Hou X, Simmet T, Shen J
Granuloma formation has been shown to be induced and elicited by schistosome egg antigens, and it finally develops into fibrosis in intestine and the liver. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans infected with schistosomes. Boswellic acid (BA)-containing extracts such as extracts of the oleogum resin from Boswellia serrata (BSE) have anti-inflammatory and immunomodulatory activity. However, little is known about the role of such extracts in schistosome egg-induced granulomatous inflammation. In order to investigate the effect of a watersoluble cyclodextrin complex preparation of BSE (BSE-CD) on Schistosoma japonicum (S. japonicum) egg-induced liver granuloma, mice infected with S. japonicum cercariae were injected with BSE-CD during egg granuloma formation. The data showed that BSE-CD significantly reduced the size of liver granuloma and levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST); however, BSE-CD treatment had no effect on worm load and egg burden. The data also showed that BSE-CD significantly decreased the expression of leukotriene B(4) (LTB(4)) and prostaglandin E(2) (PGE(2)), as well as the expression of matrix metallopeptidase 9 (MMP-9) in liver both on the mRNA and protein level. Thus, BSE-CD can significantly attenuate S. japonicum egg-induced hepatic granuloma, which may be partly dependent on the downregulation of some biochemical mediators.
Parasitol Res. 2013 Mar;112(3):1105-11.
PMID: 23271565 [PubMed - indexed for MEDLINE]
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| 33. |
Boswellia serrata and Salvia miltiorrhiza extracts reduce DMN-induced hepatic fibrosis in mice by TGF-beta1 downregulation.
Sferra R, Vetuschi A, Catitti V, Ammanniti S, Pompili S, Melideo D, Frieri G, Gaudio E, Latella G
BACKGROUND: Hepatic fibrosis is characterised by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, including collagen that occurs in chronic liver diseases. Transforming growth factor-beta1 (TGF-beta)/Smad3 signalling plays a major role in tissue fibrogenesis acting as a potent stimulus of ECM accumulation.
AIM: To evaluate the effects of a combined therapy with anti-inflammatory Boswellia and anti-fibrotic Salvia extracts on the course of chronic hepatitis-associated fibrosis induced by dimethylnitrosamine (DMN) in mice, as well as on the hepatic expression of TGF-beta1 and Smad proteins.
METHODS: Chronic hepatitis-associated fibrosis was induced in mice by intraperitoneal DMN administration. Mice were assigned to 5 groups: controls; DMN without any treatment; DMN treated orally with Boswellia extracts (50 mg/kg/day); DMN treated orally with Salvia extracts (150 mg/ kg/day); DMN treated orally with both Boswellia (50 mg/kg/day) and Salvia extracts (150 mg/kg/ day). The liver was excised for macroscopic examination and histological, morphometric and immunohistochemical (IHC) analyses. For IHC, alpha-smooth muscle actin (alpha-SMA), collagen types I-III, TGF-beta1, connective tissue growth factor (CTGF), Smad3, Smad7, CD3, PCNA and TUNEL antibodies were used.
RESULTS: The combined oral administration of Boswellia and Salvia extracts improved the course and macroscopic findings of DMN-induced chronic hepatitis-associated fibrosis. The histological severity of the hepatic fibrosis showed a marked improvement following treatment and was associated with a reduction in the hepatic expression of alpha-SMA, collagen I-III, CTGF, TGF-beta1, Smad3, and Smad7.
CONCLUSIONS: These data demonstrate that co-treatment of Boswellia plus Salvia extracts is effective in preventing hepatic fibrosis in DMN-induced chronic hepatitis. The anti-fibrotic properties are mainly related to Salvia extracts and appear to be mediated by the inhibition of the TGF-beta1/Smad3 pathway.
Eur Rev Med Pharmacol Sci. 2012 Oct;16(11):1484-98.
PMID: 23111960 [PubMed - indexed for MEDLINE]
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| 34. |
Effect of hexane extract of Boswellia serrata oleo-gum resin on chemically induced liver damage.
Y J, Kamath JV, Asad M
The hexane extract of oleo-gum-resin of Boswellia serrata (BSHE) was evaluated for its effect on liver injury induced by carbon tetrachloride, paracetamol or thioacetamide. The BSHE was given in two different doses (87.5 mg/kg p.o. and 175 mg/kg p.o.). Silymarin, a known hepatoprotective agent was used as standard. The lower dose of BSHE (87.5 mg/kg p.o.) significantly reduced the elevated levels of serum marker enzymes and prevented the increase in liver weight in all three models of liver injury, while the higher dose showed mild hepatoprotective activity. The hepatoprotective effect of lower dose of BSHE was supported by changes in histopathology. It was concluded that hexane extract of oleo-gum-resin of Boswellia serrata plant in lower doses possess hepatoprotective activity.
Pak J Pharm Sci. 2006 Apr;19(2):129-33.
PMID: 16751123 [PubMed - indexed for MEDLINE]
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