Two new polyhydroxy polyacetylenes, herpecaudenes A and B (1 and 2), were isolated from the ethanol extract of fruits of Herpetospermum caudigerum, an important Tibetan medicine. The structures of them were elucidated on the basis of extensive spectroscopic methods including UV, IR, HRESIMS, 1H and 13C NMR, HMBC, HSQC, and 1H-1H COSY. Compound 2 showed significant inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages with IC50 values of 7.05 ± 1.59 µM.
Oxidative stress has been suggested to play a causative role in the development of obesity-induced insulin resistance and type 2 diabetes. Given the antioxidant potency of previously reported xanthones isolated from <i>Swertia mussotii</i>. These natural products were further evaluated against other targets in diabetes, aldose reductase and α-glucosidase, in order to identify novel multitarget-directed antidiabetic agents. Among the 14 xanthones screened, 1,3,7,8-tetrahydroxyxanthone (<b>6</b>), 1,3,5,8-tetrahydroxyxanthone (<b>7</b>), and 2,3,6,8-tetrahydroxyxanthone-7C-(β-D-glucoside) (<b>12</b>) were confirmed as good antioxidants and α-glucosidase inhibitors. Xanthone <b>7</b> was also confirmed as a potent inhibitor of aldose reductase (ALR2). Xanthone <b>7</b> was the most active α-glucosidase and ALR2 inhibitor, with IC<sub>50</sub> values of 5.2±0.3 μM and 88.6±1.6 nM, respectively, while compound <b>12</b> was shown to be the most active antioxidant. Given the overall profile, xanthone <b>7</b> is considered to be the most promising multitarget antidiabetic agent, and may have potential for the treatment of both diabetes and diabetic complications.<br><b>Nature′s medicine cabinet:</b> Xanthones isolated from <i>Swertia mussotii</i> were evaluated as multitarget antidiabetic agents. 1,3,5,8-Tetrahydroxylxanthone was identified as a good antioxidant, and also exhibited potent inhibition of α-glucosidase and aldose reductase, proven targets in the treatment of diabetes.
"The ancient art of Tibetan medicine is a veritable treasure in the world annals of medical science. Tibetan medicine evolved over ages, as the Tibetan people accumulated experience struggling against the conditions of the snow plateau, emerging as a unique realm of medicine with a distinct understanding of physiology and pathology and its own methods of diagnosis, treatment and medication. The abundant medicinal herbs that grow on the plateau are the active ingredients in the special medicines Tibetans use to treat patients, which in turn is a precious cultural legacy that is now being passed on to the world. Known for its traditional therapies, Tibetan medicine is remarkably effective and beneficial, and has made great contributions to the overall health of humankind"--Container.
Mercury sulfides are used in Ayurvedic medicines, Tibetan medicines, and Chinese medicines for thousands of years and are still used today. Cinnabar (α-HgS) and metacinnabar (β-HgS) are different from mercury chloride (HgCl2) and methylmercury (MeHg) in their disposition and toxicity. Whether such scenario applies to weanling and aged animals is not known. To address this question, weanling (21d) and aged (450d) rats were orally given Zuotai (54% β-HgS, 30mg/kg), HgS (α-HgS, 30mg/kg), HgCl2 (34.6mg/kg), or MeHg (MeHgCl, 3.2mg/kg) for 7days. Accumulation of Hg in kidney and liver, and the toxicity-sensitive gene expressions were examined. Animal body weight gain was decreased by HgCl2 and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2 and MeHg produced dramatic tissue Hg accumulation, increased kidney (kim-1 and Ngal) and liver (Ho-1) injury-sensitive gene expressions, but such changes are absent or mild after Zuotai and HgS. Aged rats were more susceptible than weanling rats to Hg toxicity. To examine roles of transporters in Hg accumulation, transporter gene expressions were examined. The expression of renal uptake transporters Oat1, Oct2, and Oatp4c1 and hepatic Oatp2 was decreased, while the expression of renal efflux transporter Mrp2, Mrp4 and Mdr1b was increased following HgCl2 and MeHg, but unaffected by Zuotai and HgS. Thus, Zuotai and HgS differ from HgCl2 and MeHg in producing tissue Hg accumulation and toxicity, and aged rats are more susceptible than weanling rats. Transporter expression could be adaptive means to reduce tissue Hg burden.
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