Evaluation of the in vitro and in vivo anti-inflammatory activity of Gymnosporia montana (Roth). Benth leaves.

ETHNO-PHARMACOLOGICAL RELEVANCE: Gymnosporia montana (Roth) Benth an herbaceous shrub used in Indian traditional medicine their leaves decoction was used as mouthwash to get relieve from toothache, hence it is also known as Dantakashta in Sanskrit language which means the plant used for tooth problems. Traditionally the leaves juice used to alleviate inflammation and in some parts of India like Saurashtra in Gujarat, leaves were chewed as a folklore cure for Jaundice and in Bhandra region Karnataka, leaves extract mixed with cow milk used for jaundice. Hepatoprotective activity for G. montana leaves was well reported however, its use for inflammation and toothache are still not studied to investigate active phytoconstituents responsible for anti-inflammatory activity. AIM OF THE STUDY: The present study aimed at bioactivity guided isolation of G. montana leaves extracts using inhibition of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukins (IL-1ß and IL-6) in RAW 264.7 cells in vitro assay to yield bioactive phytoconstituents. MATERIALS AND METHODS: The n-hexane, ethyl acetate and methanol extracts prepared from G. montana leaves were evaluated for cell viability using MTT assay. The effect of extracts to inhibit the pro-inflammatory mediators like NO, TNF-α, IL-1ß and IL-6 in RAW 264.7 macrophages was measured by enzyme-linked immunosorbent assay (ELISA). The quantitative analysis of the isolated phytoconstituents was performed using quantitative Nuclear Magnetic Resonance (qNMR). RESULTS: The n-hexane, ethyl acetate, and methanol extracts of G. montana leaves exhibited cell viability in the range of 97.43-84.88% at 50 µg/mL concentration in RAW 264.7 macrophages. In-vitro evaluation of extracts showed that n-hexane extract was most effective in inhibiting NO, TNF-α, IL-1ß and IL-6 inflammatory mediators at 50 µg/mL in lipopolysaccharides (LPS) stimulated RAW 264.7 cells. Further n-hexane extract, its fraction GMHA3 and ß-amyrin exhibited significant anti-inflammatory activity at 100, 50 and 30 mg/kg per oral, respectively in carrageenan-induced rat paw edema. The quantitative analysis by qNMR revealed ß-amyrin as a major compound in the n-hexane extract. CONCLUSIONS: In vitro and in vivo bioassay results suggested that G. montana n-hexane extract, its fraction GMHA3 and ß-amyrin exhibits significant anti-inflammatory activity proves the traditional uses of G. montana leaves. The reported activity of ß-amyrin for periodontitis provides evidence of profound the use of G. montana leaves for toothache and anti-inflammatory activity.

Natural Product Inhibitors of Cyclooxygenase (COX) Enzyme: A Review on Current Status and Future Perspectives.

BACKGROUND: Several clinically used COX-1 and COX-2 inhibitor drugs were reported to possess severe side effects like GI ulcers and cardiovascular disturbances, respectively. Natural products being structurally diverse always attracted the attention of chemists/ medicinal chemists as a potential source of lead molecules in the drug discovery process. COX-2 inhibitory natural products also possess potential cancer chemopreventive property against various cancers including that of colon, breast and prostate. METHODS: Various in vitro, in vivo and in silico standardized methods were used to evaluate COX inhibition property of different secondary metabolites isolated from plant, microbial and marine origin. RESULTS: We had earlier reported a detailed account of natural product inhibitors of COX reported during 1995-2005, in 2006. In the proposed review, we report 158 natural product inhibitors of COX during 2006 to 2019 belonging to various secondary metabolite classes such as alkaloids, terpenoids, polyphenols as flavonoids, chromones, coumarins, lignans, anthraquinones, naphthalenes, curcuminoids, diarylheptanoids and miscellaneous compounds of plant and marine origin. Further Structure Activity Relationship (SAR) studies of possible leads are also included in the article. CONCLUSION: COX inhibitors served as a potential source of lead molecules for the discovery and development of anti-inflammatory drugs. Compilation of natural product and semisynthetic inhibitors of COX may serve as valuable information to the researchers who are looking for possible lead molecules from a natural source to conduct further preclinical and clinical studies.