55-Week Treatment of Mice with the Unani and Ayurvedic Medicine Pomegranate Flower Ameliorates Ageing-Associated Insulin Resistance and Skin Abnormalities

PPARs play a pivotal role in regulating lipid and glucose homeostasis and are involved in diverse biological activities in skin. Pomegranate flower (PGF, an antidiabetic therapy in Unani and Ayurvedic medicines) has been previously demonstrated to activate both PPARalpha/gamma. Here, we found that treatment of mice with the diet containing PGF powder over 55 weeks attenuated ageing-induced abnormal increases in the homeostasis model assessment of insulin resistance, glucose concentrations during oral glucose tolerance test, and adipose insulin resistance index. The diet tended to decrease the excessive peri-ovary fat mass. It, however, increased the thinned subcutaneous fat thickness. In addition, the diet restored decreases in skin water content, epidermis thickness, and collagen density in corium. Thus, our results demonstrate that long-term treatment with the Unani and Ayurvedic therapy ameliorates ageing-induced insulin resistance, which is associated with reversal of ageing-induced fat redistribution. Further, PGF attenuates ageing-mediated undesirable skin abnormalities

The Ayurvedic Medicine Salacia oblonga Attenuates Diabetic Renal Fibrosis in Rats: Suppression of Angiotensin II/AT1 Signaling

In human diabetic nephropathy, the extent of tubulointerstitial fibrosis is the leading cause of end-stage renal disease; fibrosis is closely correlated with renal dysfunction. Although a wide array of medicinal plants play a role in the prevention and treatment of diabetes, there are few reports of the application of herbal medicines in amelioration of renal fibrosis, or the underlying mechanisms by which such benefits are mediated. The efficacy of the Ayurvedic antidiabetic medicine Salacia oblonga (SO) root on rat renal fibrosis was investigated. An aqueous extract from SO (100 mg/kg, p.o., 6 weeks) diminished renal glomerulosclerosis and interstitial fibrosis in Zucker diabetic fatty (ZDF) rats, as revealed by van Giesen-staining. SO also reduced renal salt-soluble, acid-soluble and salt-insoluble collagen contents. These changes were accompanied by normalization of hypoalbuminemia and BUN. Gene profiling revealed that the increase in transcripts encoding the glomerulosclerotic mediators collagen I, collagen IV, fibronectin, angiotensin II type 1 receptor (AT1), transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1 observed in ZDF rat kidney was suppressed by SO. In rat-derived mesangial cells, similar to the effect of the AT1 antagonist telmisartan, SO and its major component mangiferin suppressed the stimulatory effect of angiotensin II on proliferation and increased mRNA expression and/or activities of collagen I, collagen IV, fibronectin, AT1, TGF-β1 and PAI-1. Considered together the present findings demonstrate that SO attenuates diabetic renal fibrosis, at least in part by suppressing anigiotensin II/AT1 signaling. Further, it now emerges that mangiferin is an effective antifibrogenic agent

Improvement of Liquid Fructose-Induced Adipose Tissue Insulin Resistance by Ginger Treatment in Rats Is Associated with Suppression of Adipose Macrophage-Related Proinflammatory Cytokines

Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of “lipotoxicity.” Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage) for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS)-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines

Pomegranate flower : a unique traditional antidiabetic medicine with dual PPAR-α/-γ activator properties

PPARs are transcription factors belonging to the superfamily of nuclear receptors. PPAR-α is involved in the regulation of fatty acid (FA) uptake and oxidation, inflammation and vascular function, while PPAR-γ participates in FA uptake and storage, glucose homeostasis and inflammation. The PPARs are thus major regulators of lipid and glucose metabolism. Synthetic PPAR-α or PPAR-γ agonists have been widely used in the treatment of dyslipidaemia, hyperglycaemia and their complications. However, they are associated with an incidence of adverse events. Given the favourable metabolic effects of both PPAR-α and PPAR-γ activators, as well as their potential to modulate vascular disease, combined PPAR-α/-γ activation has recently emerged as a promising concept, leading to the development of mixed PPAR-α/-γ activators. However, some major side effects associated with the synthetic dual activators have been reported. It is unclear whether this is a specific effect of the particular synthetic compounds or a class effect. To date, a medication that may combine the beneficial metabolic effects of PPAR-α and PPAR-γ activation with fewer undesirable side effects has not been successfully developed. Pomegranate plant parts are used traditionally for the treatment of various disorders. However, only pomegranate flower has been prescribed in Unani and Ayurvedic medicines for the treatment of diabetes. This review provides a new understanding of the dual PPAR-α/-γ activator properties of pomegranate flower in the potential treatment of diabetes and its associated complications