PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women. Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0.5%); PCOS group administered with letrozole (1 mg/kg) dissolved in solution (CMC 0.5%); Metformin group given with metformin (20 mg/kg) + letrozole (1 mg/kg); and Quercetin group provided with quercetin (30 mg/kg) + letrozole (1 mg/kg). All doses were given orally via gavage, for 21 consecutive days and colpocytological analysis was carried till end. After 21rst day, blood was taken out, centrifuged and plasma was kept for biochemical analysis (ELISA, anti-oxidant enzymes, lipid profile) and the reproductive organs were dissected out for histopathological evaluation. Quercetin as a chief member of flavonoid, showed beneficial effects by decreasing body weight, ovarian diameter, cysts and restoring healthy follicles, follicle’s extra-glandular layers, and corpora lutea in contrast to the positive control. Additionally, lipid profile and anti-oxidant status were also maintained to baseline which was very high in diseased rats (p < 0.001).Quercetin depicted a mark regulation in steroidogenesis by decreasing the levels of testosterone (0.78 ng/ml ± 0.14 in quercetin vs. PCOS positive control 1.69 ng/ml ± 0.17, p < 0.001) and estradiol (8.85 pg/ml ± 0.19 in quercetin vs. PCOS positive 1.61 pg/ml ± 0.29) and increasing progesterone levels (34.47 ng/ml ± 1.65 in quercetin vs. 11.08 ng/ml ± 1.17 in PCOS positive). The effects of quercetin were moderately parallel to the standard drug available in market i.e. metformin. The present study has confirmed that quercetin has the potentials to alleviate the hormonal and metabolic disturbances occurring in PCOS.
1 September 2020 in Saudi Journal of Biological Sciences
Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.
Background: New approaches for the prevention of colon cancer perseveres an essential necessity. Though, resistance to existing chemo-preventive drugs is moderately predominant in colon carcinogenesis. Taxifolin (dihydroquercetin) is a flavononol, have shown virile biological activities against few cancers. The current study was designed to investigate and equate antitumor activity of Taxifolin (TAX) in colorectal cancer cell lines and in HCT116 xenograft model in a comprehensive approach. Methods: Two human colorectal cancer cell lines HCT116 and HT29, were used. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MMT) protocol was performed to elucidate the impact of TAX and β- catenin inhibitor (FH535) on the viability of HCT116 and HT29 cell lines. Apoptosis /cell cycle assay was performed. Data interpretation was done with a FACScan (Becton Dickinson, NJ). About 1 × 10 4 cells per sample were harvested. Histograms of DNA were analyzed with ModiFitLT software (verity Software House, ME, USA). Western blotting and RT-PCR were performed for protein and gene expression respectively in in vitro and in vivo . Results: We found that TAX induced cytotoxicity in colorectal cells in a dose-dependent manner and time dependent approach. Further, our data validated that administration of TAX to human colorectal cancer HCT116 and HT29 cells resulted in cell growth arrest, variation in molecules controlling cell cycle operative in the G2 phase of the cell cycle and apoptosis in a concentration dependent approach. Further our results concluded that TAX administration decreases expression of β-catenin gene , AKT gene and Survivin gene and protein expression in in vitro and in vivo . Conclusion: Our findings proposed that targeting β-catenin gene may encourage the alterations of cell cycle and cell cycle regulators. Wnt/ β-catenin signaling pathway possibly takes part in the genesis and progression of colorectal cancer cells through regulating cell cycle and the expression of cell cycle regulators.
29 April 2015 in BMC Complementary and Alternative Medicine
Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles. Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, 1H NMR, 13C NMR and 2D NMR spectroscopic analyses, and also by comparison with reported literature. Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p < 0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E2 (PGE2) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica. These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The study was commenced to assess the favorable effects of Rutin against metabolic, biochemical, histological, and androgenic aspects of polycystic ovary syndrome in rats. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) per orally (p.o) for a period of 21 days for the induction of PCOS, followed by dose of rutin (100 mg/kg and 150 mg/kg, p.o) for 15 days using 0.5% w/v CMC as vehicle. Metformin was also given as a standard control to one of the rat groups. Serum estradiol, progesterone, testosterone, serum lipid parameters, CRP and glucose levels were evaluated. Furthermore, antioxidant activity was tested using superoxide dismutase, catalase, glutathione per-oxidase and reactive-oxygen species level. Rutin flavonoid had a dose-dependent effect on androgenic levels depicting more recovery in the rutin-I treated group, while rutin-II treated groups showed better antioxidant and lipid profiles as compared with PCOS groups. A decrease in the value of C reactive protein (CRP) and a restoration in the proportion of estrous phase smears were observed in the rutin treated groups. Histopathological examination of ovary revealed a significant decrease in the number of cystic follicles in post treated groups. The effects observed with rutin were moderately similar to that with standard metformin, a widely used treatment drug for PCOS. The study provides evidence for the potential ameliorative effects of rutin against clinical and biochemical features of PCOS.
Cisplatin (CP), an effective anticancer agent, carries the risk of impairing testicular function leading to infertility. The present study aimed at evaluating the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP-induced oxidative stress and testicular injuries in rats. Rats were divided into six groups (n = 6). Group I (control), group II (CP single dose on day 16). Group III received AHE for 21 days. Group IV (CP + AHE; post- treatment group). Group V (AHE + CP; pre-treatment group) and group VI (CP + Sily). CP treatment reduced serum testosterone (T), LH and FSH, decreased the activity level of antioxidant enzymes while increased the concentration of oxidative stress markers, i.e. thiobarbituric acid reactive substances (TBARS), H2O2 and nitric oxide (NO) along with corresponding DNA damages. Furthermore, CP induced adverse morphological changes in testis of rats including reduced epithelial height and tubular diameter, increased luminal diameter with impaired spermatogenesis. Pre and post-treatment with AHE reduced the side effects of CP in testis tissues through improvement in the reproductive hormonal secretions, enzymatic activities, histological and DNA damage parameters. Pretreatment seems to be more effective and equivalent to silymarin group in reversing the CP deleterious effects as compared to post-treatment. The results demonstrated that A. hydaspica treatment in CP-induced testicular toxicity augments the antioxidants defense mechanism, reverted the level of fertility hormones, suppressed the histomorphological alterations and DNA damages and thus provides the evidence that it may have a therapeutic role in free radical mediated diseases.