8.2.4 Atemwege

The research examined the effects of extracts (BSE) on a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). The severity and progression of MIA-induced osteoarthritis were assessed using microcomputed tomography imaging. Additionally, the study investigated the impact of BSE various the biomarkers associated with osteoarthritis, including anabolic and catabolic factors, pro-inflammatory factors, and apoptosis factors. The evaluation methods employed included western blot, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction analysis in osteoarthritic rats. Supplementing osteoarthritic rats with BSE reduced tissue injury, cartilage destruction, and decreased in MIA-induced roughness on the articular cartilage surface. MIA-treated rats exhibited increased expressions of phosphorylation of Smad3, MMPs, p-IκB, p-NF-κB, and pro-inflammatory factors (IL-1β, IL-6, TNF-α, and COX-2), which were mitigated by BSE supplementation. Furthermore, protein expressions related to apoptosis pathways were significantly reduced in MIA-induced rats supplemented with BSE. These findings suggested that BSE ingestion may enhance the inflammatory response, decrease JNK-dependent MMPs activation, and alleviate caspase-3-dependent apoptosis in MIA-induced osteoarthritic rat models. Consequently, BSE exhibits potential as a therapeutic agent for treating osteoarthritis.

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OBJECTIVE: Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells.

MATERIALS AND METHODS: The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF).

RESULTS: AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G/G phase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins.

CONCLUSION: AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.

A study was conducted to evaluate mucoadhesive property and immunomodulatory effect of phytogenic gums from and on intranasal Peste des petits ruminants (PPR) vaccination in goats and sheep in an ex-vivo and in-vivo situations. Plant gums were purified, dried and compressed into 500gm tablets. Modified shear stress measurement technique was used on freshly excised trachea and intestine tissues of goat to measure peak adhesion time. Forty eight animals (24 goats and 24 sheep) were divided into eight groups (of 3 goats and 3 sheep) and immunized intranasally with gum-vaccine combinations in two ratios (1:1, 1:2). Antibody against PPR virus was measured on day 14, 28, 42 and 56 post vaccination using H-based PPR bELISA. The peak adhesion time of the different gums was transient. PPR virus antibodies were detected in all immunized goats and sheep but not in unvaccinated control. The best percentage inhibition was recorded for Boswellia carteri-vaccine combination group at a ratio of 1:1. Administration of -PPR vaccine combination through intranasal or subcutaneous route, elicited similar antibody titre, implying that the intranasal route may be used as a non-invasive alternative delivery in PPR vaccination of small ruminants.

BACKGROUND: Purified fractions from a Boswellia serrata Roxb. Ex. Colebr. (Burseraceae) extract (ETOH and DCM) contain biologically active compounds that are well known for having inflammation inhibitory properties. In this work, the purified fractions were tested in-vitro for LTC, LTA and COX-2 activities using ELISA and qPCR was performed to determine gene regulation in human leukemia (HL-60) Cells. Two D-imaging tomography was performed to determine the anti-inflammatory activities of the fractions in BALB/c mouse model of lung inflammation.

OBJECTIVE: To evaluate anti-inflammatory activities of bioactive compounds of Boswellia serrata purified fractions.

METHODS: In-vitro MTT assay was performed in HL-60 cell lines for measuring the toxicity/ viability of the cells. ELISA tests were performed for evaluating LTA, LTC and COX-2 activities. qPCR was performed to evaluate the expression of mRNA in HL-60 cells. In-vivo experiments were performed in OVA sensitized and challenged BALB/c mice at two doses of Boswellia serrata purified fraction containing 6% Boswellic acid of 50 and 100mg/kg body weight were given orally and the standard drug dexamethasone (DXA, 4 mg/kg body weight) and reduction in lung inflammation was assessed by using an IVIS Xenogen in-vivo fluorescence imaging system.

RESULTS: A purified fraction of Boswellia serrata ETOH extracts reduced leukotriene-C-synthase activity by 52%, leuktotriene-A-hydrolase activity by 22% and COX-2 activity by 99% with an IC50 of 12.5μg/ml. Intragastric administration of the purified fraction of Boswellia serrata at two doses of 50mg/kg b.w. and 100mg/kg b.w., respectively along with 2-3% HPMC resulted in a ~51% (P value <0.01) reduction in OVA induced lung inflammation in BALB/c mice as observed by imaging tomography. Treatment of the OVA challenged mice with standard drug dexamethasone (DXA) reduced inflammation by ~66% with significant value (P<0.0001).

CONCLUSION: The present study describes that Boswellia serrata ethanolic extracts purified fraction (ETOH-BS) possess significant anti-inflammatory activities in HL-60 and in BALB/c and further supports for its use as Ayurvedic medicines traditionally in the treatment of lung disorders including allergy and asthma.

Nowadays, only a little part of essential oils produced at an industrial level is employed for insecticidal formulations, while thousand tons are used for perfumery purposes. This research explores the insecticidal potential of two essential oils largely used in perfumery, ylang ylang () and frankincense ( spp.) on three insects of economic importance, , and comparing their performances with a commercial pyrethrum extract. GC-MS showed that the ylang ylang and frankincense essential oils were mainly composed of α-thujene (73.8%), benzyl salicylate (24.4%) and linalool (21.9%), respectively. Ylang-ylang and frankincense essential oils showed significant insecticidal activity against . larvae (LC < 70 ppm) and . adults (LD < 80 µg/female), respectively, while no relevant toxicity was detected on . . As highly available from the fragrance industry, these essential oils may be further considered as promising ingredients to be used in botanical formulations against mosquitoes and houseflies.

Membrane fluidity is the most important physiochemical property of cell membranes and governs its functional attributes. The current investigations were undertaken to understand the potential role of acetyl-11-keto-β-boswellic acid (AKBA), if any, on regulation of membrane dynamics under conditions of benzo(a)pyrene (BaP)-induced lung carcinogenesis in female rats. The animals were divided into five groups which included (I) Normal control, (II) Vehicle treated (olive oil), (III) BaP treated, (IV) AKBA treated and (V) BaP + AKBA treated. BaP was administered at a dose level of 50 mg/kg b.wt. in olive oil orally twice a week for 4 weeks. AKBA was given at a dose level of 50 mg/kg b.wt. in olive oil orally thrice a week for 24 weeks. In addition, AKBA was also administered at a similar dose to BaP-treated animals 4 weeks prior to BaP administration and continued for another 20 weeks. The lipid profile and membrane dynamics were analysed in lung tissue. Total lipids, phospholipids content, membrane fluidity, polarization and order of membrane were significantly (p ≤ 0.001) increased in BaP-exposed animals. However, significant decrease was observed in glycolipids, cholesterol, microviscosity and anisotropy levels compared with normal control animals. Appreciable improvements in above indices were recorded when AKBA was administered to BaP-treated animals. Moreover, the structural variations observed in Fourier-transform infrared spectroscopy spectrum were also normalized in BaP-treated rats with AKBA supplementation. This suggests that the AKBA has a potential role in improving membrane fluidity and associated lipid content in BaP-induced lung carcinogenesis.

To study the role of boswellic acid in reducing asthma phenotype severity and the relationship between the expression of pSTAT6 and GATA3, thirty-six mice were randomly divided into normal control group, asthma group, and boswellic acid group (treatment group). The asthma model was established through an intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel at 88.67 mg/mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in peripheral blood were detected by reverse transcription-polymerase chain reaction and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic group were significantly higher than in the normal control group; they were markedly lower in the treatment group than the asthma group, and there was no significant difference when compared with the normal control group. The pSTAT6 expressions in the asthma, control and treatment groups were 2.256 ± 0.125, 0.524 ± 0.210, and 0.897 ± 0.134 at gray level, respectively. The GATA3 expressions in the asthma, control, and treatment groups were 3.521 ± 0.631, 0.435 ± 0.136, and 0.743 ± 0.149 at gray level, respectively. pSTAT6 and GATA3 expression levels were similar in the treatment and control groups. GATA3 expression had a positive correlation with pSTAT6 expression. Boswellic acid may improve asthma symptoms by inhibiting pSTAT6 expression, which consequently reduces GATA3 expression.

Asthma is a serious global health problem characterised by airway inflammation, airway epithelial wall shedding, enhanced mucus production, increased IgE levels and airway hyperresponsiveness. The pathophysiology of asthma is mediated by Th2 cells which produce Th2 cytokines like interleukin-4, interleukin-5, interleukin-13 and interleukin-9. The differentiation of Th2 cells is induced by the transcription factor GATA3 which is activated by pSTAT6 via IL-4 signalling. To investigate the anti-asthmatic potential of Boswellic acid, as well as the underlying mechanism involved, we studied its anti-asthmatic potential in a murine model of asthma. In this study, BALB/c mice were systemically sensitized by ovalbumin (OVA) followed by aerosol allergen challenges. We investigated the effect of Boswellic acid on airway hyperresponsiveness, inflammatory cell infiltration, Th2 cytokine and OVA-specific IgE production in a mouse model of asthma. We found that Boswellic acid treated groups suppressed allergic airway inflammation, AHR, OVA-specific IgE and Th2 cytokines secretion. It also suppressed the expression of pSTAT6 and GATA3 in a dose dependent manner. Our data suggest that the mechanism by which Boswellic acid effectively treats asthma is based on reductions of Th2 cytokines via inhibition of pSTAT6 and GATA-3 expression.

BACKGROUND: Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract in an experimental model of pulmonary fibrosis using bleomycin (BL).

METHODS: Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior to administration of BL or gamma irradiation or both. BL (0.15 U/rat) in 25 μl of 0.9% normal saline (NS) or 0.9% NS alone was administered intratracheally. Rats were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week) with a gamma cell-40 (Cesium-137 irradiation units, Canada) during the last two weeks of the experiment. BA was administered during BL or irradiation treatment or both. After the animals were sacrificed, bronchoalveolar lavage was performed; lungs were weighed and processed separately for biochemical and histological studies.

RESULTS: In rats treated with BL, levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were significantly elevated (P = 0.05 and P = 0.005). Hydroxyproline was highly and extensively expressed. Immunoreactive compounds were abundantly expressed, represented in the levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in the lung as well as the aggregation of fibroblasts in the fibrotic area. The levels of lipoxygenase enzyme activity were significantly increased (P = 0.005). Antioxidant activities measured in BL-treated rats deteriorated, coupled with the elevation of both levels of plasma lipid peroxide (LP) content and bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had reduced number of macrophages, (P = 0.01), neutrophils in bronchoalveolar lavage (P = 0.01) and protein (P = 0.0001). Moreover, the hydroxyproline content was significantly lowered in BA-treated rats (P = 0.005). BA extract inhibited the TGF-ß induced fibrosis (P = 0.01) and 5-LOX activity levels (P = 0.005).Histologically, BA reduced the number of infiltrating cells, ameliorated the destruction of lung architecture and attenuated lung fibrosis.

CONCLUSION: BA attenuates the BL-induced injury response in rats, such as collagen accumulation, airway dysfunction and injury. This study suggests that the blocking of 5-LOX may prevent the progression of fibrosis.

OBJECTIVE: Impacts of air pollution on the human health have been recognized over the last decades. Smokes, in particular, have deleterious effects on the respiratory system. According to a local tradition, incense "Bakhour" is burnt and the resultant heavy smokes are inhaled. The objective of the present study is to investigate the ultrastructural pulmonary changes which can be induced by Arabian incense, Bakhour, exposure.

METHODS: The study was conducted from September through to December 2003, at the Animal House, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. Two groups of Wister albino rats, Rattus norvegicus, were used. One group (n=16) was exposed to 420 grams of Bakhour for 14-weeks at the rate of 4 grams/day in the exposure chamber. Additional group of rats, of equal number, was used as non-exposed control. At the end of the exposure period, lung tissues were removed from all experimental animals and processed for electron microscopy.

RESULTS: Alveolar pneumocytes of exposed animals revealed significant ultrastructural changes which involved the cell organelles and surfactant material of type II cells. Hyperplasia of alveolar cells was a feature in the affected lung tissue. Neutrophils were recognized infiltrating pulmonary alveoli and accompanied with degenerative and necrotic changes of the alveolar cells. Deposition of collagen fibrils in the alveolar walls was also observed.

CONCLUSION: Basing upon the results of electron microscopy, it was concluded that exposure to Bakhour can induce ultrastructural pulmonary changes which may imply compromised respiratory efficiency.

The involvement of human leukocyte elastase (HLE) in several inflammatory processes and the reported inhibitory effect of ursolic acid on HLE has prompted the authors to start investigation on the effects of acetyl-11-keto-β-boswellic acid (AKBA) on serine proteinases including HLE.