Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data.

BACKGROUND: Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data. PURPOSE: We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis. METHODS: Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN. RESULTS: This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-ß1, TGF-ß1 mRNA, CTGF and IL-1ß, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1ß, TGF-ß1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks. CONCLUSIONS: Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.

Tanshinone IIA and its derivative activate thermogenesis in adipocytes and induce "beiging" of white adipose tissue.

Tanshinone IIA (TAN2A) is a major active ingredient of Salvia miltiorrhiza used in traditional Chinese medicine and tanshinone 20 (TAN20) is a derivative of TAN2A. In this study, we examined the effects of TAN2A and TAN20 on adipogenesis, lipid metabolism, and thermogenesis. Our experiments showed that both TAN2A and TAN20 increased mitochondria content in adipose tissue, enhanced energy expenditure, reduced body weight, and improved insulin sensitivity and metabolic homeostasis in obese and diabetic mouse models. We demonstrated that TAN20 can facilitate the transformation from white to beige adipose tissue, as well as activate brown adipose tissue. In uncoupling protein 1 (UCP1) knockout mouse model, the effects of TAN2A and TAN20 on body weight and glucose tolerance were not observed, suggesting that such effects were UCP1 dependent. Furthermore, we found that TAN2A and TAN20 increased the expression of UCP1 and other thermogenic genes in adipocytes through AMPK-PGC-1α signaling pathway. Our findings indicate that TAN2A and its derivative TAN20 are potential interesting energy expenditure regulators and may be implicated in treatment of obesity and other metabolic disorders.

Prospects for improving cosmological parameter estimation with gravitational-wave standard sirens from Taiji.

Taiji, a space-based gravitational-wave observatory, consists of three satellites forming an equilateral triangle with arm length of 3×106 km, orbiting around the Sun. Taiji is able to observe the gravitational-wave standard siren events of massive black hole binary (MBHB) merger, which is helpful in probing the expansion of the universe. In this paper, we preliminarily forecast the capability of Taiji for improving cosmological parameter estimation with the gravitational-wave standard siren data. We simulate five-year standard siren data based on three fiducial cosmological models and three models of MBHB's formation and growth. It is found that the standard siren data from Taiji can effectively break the cosmological parameter degeneracies generated by the cosmic microwave background (CMB) anisotropies data, especially for dynamical dark energy models. The constraints on cosmological parameters are significantly improved by the data combination CMB + Taiji, compared to the CMB data alone. Compared to the current optical cosmological observations, Taiji can still provide help in improving the cosmological parameter estimation to some extent. In addition, we consider an ideal scenario to investigate the potential of Taiji on constraining cosmological parameters. We conclude that the standard sirens of MBHB from Taiji will become a powerful cosmological probe in the future.