Tectona grandis leaf extract ameliorates hepatic fibrosis: Modulation of TGF- ß /Smad signaling pathway and upregulating MMP3/TIMP1 ratio.

ETHNOBOTANICAL RELEVANCE: Tectona grandis L.f (or syn: Jatus grandis (L.f.) Kuntze Revis), from family Lamiaceae, also known as Teak, is widely recognized in ayurvedic system of medicine and confer curative potential against inflammation, liver disorders, biliousness, diabetes, bronchitis, leprosy and dysentery. Its leaves are rich source of edible food colorant and reported nontoxic for liver and various organs. AIM OF STUDY: Hepatic injury progression to liver cirrhosis and cancer is a serious health issue across the world. Currently, anti-fibrotic therapeutic options are limited and expensive with no FDA approved direct anti-hepato-fibrotic drug validated in clinic. Thus, the aim of this study was to understand ameliorative effect of Tectona grandis L.f, leaves in early liver fibrosis. METHOD AND RESULTS: C57BL/6 mice suffering from CCl4 induced liver injury, were orally administered at three different doses (50, 100 & 200 mg/kg) of Tectona grandis L.f, leaf extract, thrice a week, up to 4 and 8 weeks. Anti-fibrotic effect was evaluated through animal body/liver weight measurements, serological tests (AST, ALT, GSH, MDA and LDH assays), tissue hydroxyproline content, and histochemical analysis (H&E, Masson trichrome, Sirius red and αSMA localization). Moreover, transcriptional and post-transcriptional expression of fibrosis associated biomarkers and TGF-ß/Smad cascade were analyzed. It was observed that 100 mg/kg dose optimally downregulated TGF-ß1/Smad2 with upregulation of Smad7 and regulated αSMA, Col 1, PDGF, TIMP1 and MMP3 expression, post 8 weeks of treatment. In addition, MMP3/TIMP1 ratio was upregulated to 0.7, 2.5 and 1.7 fold at 50 mg/kg, 100 mg/kg & 200 mg/kg treatments respectively, in comparison to untreated liver fibrosis models. The extract contains gallic acid, caffeic acid, sinapinic acid and myricetin when analyzed through high performance liquid chromatography. CONCLUSION: Tectona grandis L.f, leaves have potential to ameliorate liver fibrosis induced by CCl4 in mice via modulation of TGF-ß1/Smad pathway and upregulated MMP3/TIMP1 ratio.

Gmelina arborea- an indigenous timber species of India with high medicinal value: A review on its pharmacology, pharmacognosy and phytochemistry.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Gmelina arborea Roxb.ex Smith, a fast-growing deciduous tree belongs to the family Lamiaceae, and is an important plantation species in many tropical areas around the world. The species is naturally distributed in semi-deciduous forests in tropical/subtropical regions of South East Asia. The tree is also an important medicinal plant in the Indian Systems of Medicine. The whole plant is used in medicine. It is astringent, bitter, digestive, cardiotonic, diuretic, laxative and pulmonary and nervine tonic. It improves digestion, memory, helps overcome giddiness and is useful in burning sensation, fever, thirst, emaciation, heart diseases, nervous disorders and piles. The roots are acrid, bitter-sweet in taste, stomachic, tonic, laxative, galactagogue and antihelmintic. The flowers are sweet, refrigerant, bitter, astringent and acrid, and are used in treating leprosy and skin diseases. The fruits are acrid, sour, sweet, refrigerant, bitter, astringent, aphrodisiac, trichogenous, alterant and tonic. Fruits are edible and also used for promoting hair growth and in treating anaemia, leprosy, ulcers, constipation, leucorrhoea and colitis. The leaves are a good fodder also. The major bioactive compounds extracted from different parts of G. arborea are arboreal, verbascoside, tyrosol, iridoids, phenylpropanoid glycoside, premnazole, martynoside, iridoid glycosides, balanophonin, gmelinol, isoarboreol apigenin, umbelliferone etc. AIM OF THE REVIEW: This review provides an insight into the medicinal aspects of G. arborea. It provides the latest information on phytochemistry, pharmacological activities and traditional uses of G.arborea. MATERIALS AND METHODS: Information on G. arborea was gathered from various sources like textbooks, literature, databases such as PubMed, Science Direct, Wiley, Springer, Taylor and Francis, Scopus, Inflibnet, Sci-Finder and Google Scholar. RESULTS: Sixty-nine phytochemicals which include lignans, acylated iridoid glycosides, acylated rhamnopyranoses, flavonoids, flavones, flavone glycosides have been isolated. Many of them have been characterized for their pharmacological activity. Several researchers have identified bioactive phytochemicals like luteolin, iridoid alkaloids from the leaves, hentriacontanol and lignans such as arboreol, isoarboreol, arborone, gmelanone, gummadiol from the heartwood, flavon glycosides in roots. The extracts are reported to have wound-healing and antidiarrheal properties. Various studies demonstrated that G.arborea and its constituents possess several pharmacological activities like anti-oxidant, anti-diabetic, anti-inflammatory, antiulcer, analgesic, anti-nociceptive, anticancer and wound healing activities. CONCLUSION: G. arborea is a valuable medicinal plant used traditionally in the Indian Systems of Medicine (ISM - Ayurveda and Unani) to treat a wide variety of ailments. These phytochemicals are highly bioactive and exhibit various pharmacological activities. However, pharmacological activities of many compounds which have been identified, are yet to be understood.