| 1. |
Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell.
Vu L, Xu F, Li T, Hua Q, Kuang X, Jiang Y, Liang Y, Niu X, Chen Y, Huang C, Mo W, Wang K, Tang K, Mo J, Lu KE, Mo Y, Mo S, Yang D, Zhao J
BACKGROUND: Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues.
METHODS: Single-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU. Enrichment analysis identified pathways involved in cellular subpopulations, and pseudo-time analysis inferred cell development processes. A gene regulatory network explored the role of transcription factors in DFU progression, and a potential herbal drug-target gene interaction network was constructed.
RESULTS: In the DFU group, immune cells were activated, with notable changes in several subpopulations. ATP5E was significantly overexpressed in Naive T cells, fibroblasts, endothelial cells, and CD8 T cells in DM patients. Specific immune cell subsets, such as Naive T_RGCC, CTL_TYROBP_CL4, Mac_SLC40A1, and M1_CCL3L1, likely contribute to DFU formation through overactivation and proliferation, leading to tissue damage and ulcer exacerbation. Key genes TPP1, TLR4, and RIPK2 were identified, and 88 active ingredients in the herbal drug-target network showed strong correlations with these targets. Herbs like Angelica dahurica, Angelica sinensis, Boswellia carterii, liquorice, myrrh, and Semen armeniacae amarae were included.
CONCLUSIONS: This study offers insights into DM and DFU cytology. T cells in DFU are activated, attacking normal tissues and worsening tissue damage. The ATP5E gene may be related to the ecological remodeling of DM, and TPP1, TLR4, and RIPK2 are potential targets for DFU treatment.
Eur J Med Res. 2024 Dec;29(1):606.
PMID: 39702546 [PubMed - indexed for MEDLINE]
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| 2. |
Alpha-boswellic acid accelerates acute wound healing via NF-κB signaling pathway.
Dong F, Zheng L, Zhang X
BACKGROUND: Boswellic acids (BAs) showed promising effects in cancer treatment, immune response regulation, and anti-inflammatory therapy. We aimed to assess the roles of alpha-BA (α-BA) in treating acute wound healing.
METHODS: In vivo wound-healing models were established to evaluate the therapeutic effects of α-BA. Cell assays were conducted to assess the impact of α-BA on cellular biological functions. Western blot analysis was employed to validate the potential mechanisms of action of α-BA.
RESULTS: Animal models indicated that wound healing was notably accelerated in the α-BA group compared to the control group (P < 0.01). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) assay preliminarily suggested that α-BA may accelerate wound healing by inhibiting excessive inflammatory reactions and increasing the protein levels of growth factors. Cell function experiments demonstrated that α-BA suppressed the proliferation and migration ability of human hypertrophic scar fibroblasts (HSFBs), thereby favoring wound healing. Additionally, α-BA exerted a significant impact on cell cycle progression. Mechanistically, the protein levels of key genes in nuclear factor kappa beta (NF-κB) signaling pathway, including cyclin D1, p65, IκBα, and p-IκBα, were downregulated by α-BA.
CONCLUSIONS: α-BA demonstrated the ability to counteract the abnormal proliferation of skin scar tissues, consequently expediting wound healing. These findings suggest its potential for development as a new agent for treating acute wound healing.
PLoS One. 2024;19(9):e0308028.
PMID: 39226297 [PubMed - indexed for MEDLINE]
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| 3. |
Phytoconstituents as modulators of NF-κB signalling: Investigating therapeutic potential for diabetic wound healing.
Yadav JP, Verma A, Pathak P, Dwivedi AR, Singh AK, Kumar P, Khalilullah H, Jaremko M, Emwas AH, Patel DK
The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.
Biomed Pharmacother. 2024 Aug;177():117058.
PMID: 38968797 [PubMed - indexed for MEDLINE]
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| 4. |
The Therapeutic Potential of Essential Oils in Managing Inflammatory Skin Conditions: A Scoping Review.
Dontje AEWK, Schuiling-Veninga CCM, van Hunsel FPAM, Ekhart C, Demirci F, Woerdenbag HJ
Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree () oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain () oil, eucalyptus () oil, and cedarwood () oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kānuka () oil and frankincense ( spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.
Pharmaceuticals (Basel). 2024 Apr;17(5):.
PMID: 38794141 [PubMed - as supplied by publisher]
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| 5. |
CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.
Tong J, Li Y, Cai X, Lou F, Sun Y, Wang Z, Zheng X, Zhou H, Zhang Z, Fang Z, Ding W, Deng S, Xu Z, Niu X, Wang H
Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.
Eur J Immunol. 2023 Sep;53(9):e2350374.
PMID: 37417726 [PubMed - indexed for MEDLINE]
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| 6. |
Evaluation of the Anti-Atopic Dermatitis Effects of α-Boswellic Acid on Tnf-α/Ifn-γ-Stimulated HaCat Cells and DNCB-Induced BALB/c Mice.
Tsai YC, Chang HH, Chou SC, Chu TW, Hsu YJ, Hsiao CY, Lo YH, Wu NL, Chang DC, Hung CF
Boswellic acids, triterpenoids derived from the genus (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent's anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1β, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.
Int J Mol Sci. 2022 Aug;23(17):.
PMID: 36077254 [PubMed - indexed for MEDLINE]
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| 7. |
Allergic contact dermatitis from Boswellia carterii (frankincense) oil.
Buonomo M, Hylwa S
Contact Dermatitis. 2021 Oct;85(4):465-467.
PMID: 33963563 [PubMed - indexed for MEDLINE]
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| 8. |
Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes.
Yang S, Zhou B, Xu W, Xue F, Nisar MF, Bian C, Huang X, Yang L, Zhang Y, Bartsch JW, Zhong JL
BACKGROUND: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis.
OBJECTIVE: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes.
METHODS: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined.
RESULTS: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1.
CONCLUSIONS: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.
Skin Pharmacol Physiol. 2017;30(1):13-23.
PMID: 28142143 [PubMed - indexed for MEDLINE]
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| 9. |
A comment about the use of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma.
Fiorica F
Eur Rev Med Pharmacol Sci. 2015 Jun;19(12):2141-2.
PMID: 26166632 [PubMed - indexed for MEDLINE]
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| 10. |
Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.
Mostafa DM, Ammar NM, Basha M, Hussein RA, El Awdan S, Awad G
CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East.
OBJECTIVE: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy.
MATERIALS AND METHODS: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-β-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity.
RESULTS AND DISCUSSION: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam.
CONCLUSIONS: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.
Drug Deliv. 2015;22(6):748-56.
PMID: 24725029 [PubMed - indexed for MEDLINE]
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| 11. |
3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.
Goel A, Ahmad FJ, Singh RM, Singh GN
OBJECTIVES: The aim of this study was to develop 3-acetyl-11-keto-beta-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.
METHODS: Polymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity.
KEY FINDINGS: TEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel.
CONCLUSIONS: This study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.
J Pharm Pharmacol. 2010 Feb;62(2):273-8.
PMID: 20487208 [PubMed - indexed for MEDLINE]
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| 12. |
Targeting NF-kappa B with a natural triterpenoid alleviates skin inflammation in a mouse model of psoriasis.
Wang H, Syrovets T, Kess D, Büchele B, Hainzl H, Lunov O, Weiss JM, Scharffetter-Kochanek K, Simmet T
Psoriasis vulgaris is a common chronic inflammatory skin disease involving cytokines and an activated cellular immune system. At variance to skin from patients with atopic dermatitis or from healthy subjects, human psoriatic skin lesions exhibit strong activation of transcription factor NF-kappaB that is mainly confined to dermal macrophages, whereas only a few dendritic cells but no CD3+ lymphocytes show activated NF-kappaB. Since NF-kappaB signaling is required for the induction and/or function of many cytokines and aberrant cytokine expression has been proposed as an underlying cause of psoriasis, we investigated whether NF-kappaB targeting would affect the course of the disease in the CD18 hypomorphic (CD18(hypo)) mouse model of psoriasis. When mice with severe psoriasiform lesions were treated systemically or locally with the IkappaB kinase inhibitor acetyl-11-keto-beta-boswellic acid (AKbetaBA), NF-kappaB signaling and the subsequent NF-kappaB-dependent cytokine production as shown by the TNF-alpha production of macrophages were profoundly suppressed. Additionally, application of the compound counteracted the intradermal MCP-1, IL-12, and IL-23 expression in previously lesional skin areas, led to resolution of the abundant immune cell infiltrates, and significantly reduced the increased proliferation of the keratinocytes. Overall, the AKbetaBA treatment was accompanied by a profound improvement of the psoriasis disease activity score in the CD18(hypo) mice with reconstitution of a nearly normal phenotype within the chosen observation period. Our data demonstrate that NF-kappaB signaling is pivotal for the pathogenesis in the CD18(hypo) mouse model of psoriasis. Therefore, targeting NF-kappaB might provide an effective strategy for the treatment of psoriasis.
J Immunol. 2009 Oct;183(7):4755-63.
PMID: 19752240 [PubMed - indexed for MEDLINE]
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| 13. |
Comparison of the irritation potentials of Boswellia serrata gum resin and of acetyl-11-keto-beta-boswellic acid by in vitro cytotoxicity tests on human skin-derived cell lines.
Burlando B, Parodi A, Volante A, Bassi AM
Indian frankincense is a gum resin from Boswellia serrata of Burseraceae used in Ayurveda and Western medicine for the antinflammatory effects of boswellic acids, particularly 3-O-acetyl-11-keto-beta-boswellic acid (AKBA). We evaluated in vitro cytotoxicities of B. serrata extract and AKBA on differentiated and undifferentiated keratinocytes (HaCaT and NCTC 2544), and foetal dermal fibroblasts (HFFF2), using neutral red uptake (NRU), MTT, and DNA assays. Comparison between NRU and MTT, and between the extract and AKBA, suggested a relatively higher toxicity of both substances on lysosomes respect to mitochondria. Extract cytotoxicity on lysosomes was higher in NCTC and HFFF2 than on the more differentiated HaCaT. DNA assay showed low extract inhibition on HFFF2 proliferation, possibly due to lower growth rate, and a stronger effect on NCTC than on HaCaT, possibly related to higher proapoptotic effect on the less differentiated NCTC, as also suggested by higher AKBA toxicity on NCTC than on HaCaT. In general, gum resin and AKBA toxicities were slightly lower or higher than that of the reference compound SDS. Our in vitro model allowed to compare the sensitivities of different human skin cells to B. serrata, and indicated that the gum resin and AKBA exert moderate to low toxicity on the skin.
Toxicol Lett. 2008 Mar;177(2):144-9.
PMID: 18304763 [PubMed - indexed for MEDLINE]
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| 14. |
Boswellic acids: A leukotriene inhibitor also effective through topical application in inflammatory disorders.
Singh S, Khajuria A, Taneja SC, Johri RK, Singh J, Qazi GN
Boswellic acids (BA), a natural mixture isolated from oleo gum resin of Boswellia serrata comprised of four major pentacyclic triterpene acids: beta-boswellic acid (the most abundant), 3-acteyl-beta-boswellic acid, 11-keto-beta-boswellic acid, and 3-acetyl-11-keto-beta-boswellic acid, is reported to be effective as anti-inflammatory, immunomodulatory, anti-tumor, anti-asthmatic and in Chron's disease. It inhibits pro-inflammatory mediators in the body, specifically leukotrienes via inhibition of 5-lipoxygenase, the key enzyme of leukotriene synthesis, is the scientifically proved mechanism for its anti-inflammatory/anti-arthritic activity. All previous work on BA for its biological activity has been done through the systemic application but no pre-clinical data reported for its anti-inflammatory activity by topical application. We here by report anti-inflammatory activity of BA through this route by applying different acute and chronic models of inflammation i.e., arachidonic acid and croton oil-induced mouse ear edema, carrageenan-induced rats paw edema and adjuvant-induced developing arthritis in rats. The results of the study revealed that the effect observed through this route is in accordance to the study conducted with the systemic route, thus establishing that BA when used through topical application is as effective as through the systemic route.
Phytomedicine. 2008 Jun;15(6-7):400-7.
PMID: 18222672 [PubMed - indexed for MEDLINE]
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| 15. |
Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri.
Banno N, Akihisa T, Yasukawa K, Tokuda H, Tabata K, Nakamura Y, Nishimura R, Kimura Y, Suzuki T
Boswellic acids are the main well-known active components of the resin of Boswellia carteri (Burseraceae) and these are still dealing with the ethnomedicinal use for the treatment of rheumatoid arthritis and other inflammatory diseases. Although several studies have already been reported on the pharmacological properties, especially on the anti-inflammatory activity, of Boswellia carteri resin and boswellic acids, the ethnomedicinal importance of Boswellia carteri and its components, boswellic acids, prompted us to undertake detailed investigation on the constituents of the resin and their anti-inflammatory activity. Fifteen triterpene acids, viz., seven of the beta-boswellic acids (ursane-type) (1-7), two of the alpha-boswellic acids (oleanane-type) (8, 9), two of the lupeolic acids (lupane-type) (10, 11), and four of the tirucallane-type (12-14, 16), along with two cembrane-type diterpenes (17, 18), were isolated and identified from the methanol extract of the resin of Boswellia carteri. Upon evaluation of 17 compounds, 1-14 and 16-18, and compound 15, semi-synthesized from 14 by acetylation, for their inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds, except for 18, exhibited marked anti-inflammatory activity with a 50% inhibitory dose (ID(50)) of 0.05-0.49 mg/ear.
J Ethnopharmacol. 2006 Sep;107(2):249-53.
PMID: 16621377 [PubMed - indexed for MEDLINE]
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