Phloroglucinol inhibited glycation via entrapping carbonyl intermediates.

Advanced glycation end products (AGEs) play an important role in the pathogenesis of age-linked disorders and diabetes mellitus. The aim of this study was to assess the repurposing potential of Phloroglucinol (PHL the antispasmodic drug), as an anti-glycation agent using Fructose-BSA model. The ability of PHL to inhibit AGE formation was evaluated using AGEs formation (Intrinsic fluorescence), fructosamine adduct (NBT) and free lysine availability (TNBSA) assays. The BSA protein conformation was assessed through Thioflavin-T, Congo-Red and Circular Dichroism assays. The lysine blockade and carbonyl entrapment were explored as possible mode of action. Our data showed that PHL significantly decreased the formation of AGEs with an IC50 value of 0.3mM. The fructosamine adducts and free lysine load was found to be reduced. Additionally, the BSA conformation was preserved by PHL. Mechanistic assays did not reveal involvement of lysine blockade as underlying reason for reduction in AGEs load. This was also supported by computational data whereby PHL failed to engage any catalytic residue involved in early fructose-BSA interaction. However, it was found to entrap the carbonyl moieties. In conclusion, the PHL demonstrated anti-glycation potential, which can be attributed to its ability to entrap carbonyl intermediates. Hence, the clinically available antispasmodic drug, presents itself as a promising candidate to be repurposed as anti-glycation agent.

Phloroglucinol ameliorated methylglyoxal induced harmful effects in rats.

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug.

The Effects of Ficus carica on Male and Female Reproductive Capabilities in Rats.

The basic purpose of pharmacology is to look into the benefits of natural remedies and make them available to the general populace. Herbal medicines are now considered to be the future of humanity. The current study explored the effects of Ficus carica (FC) extract in rats of two-generation F0 (parents) and F1 (offspring) in either sex. The F. carica extract was initially tested for acute and sub-chronic toxicity. Extracts were also tested for fertility assessment and effects on reproductive hormones like follicle-stimulating hormone (FSH), luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), estradiol, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone-sulfate (DHEAS), insulin, progesterone, and prolactin. The antioxidant activity of the extract was also evaluated by testing mRNA expressions of SOD2, GPX1, CAT, and GR in male testes and female ovaries. The animals treated with 100 mg/kg FC extract produced a more pronounced fertility effect in both genders. Expression of CAT, SOD2, GPX1, and GR was found to be increased in the reproductive organs of both sexes. Histology of the testes reveals increased spermatogenesis and increased folliculogenesis in ovaries. The hormone profile showed an increase in FSH, DHT, estradiol, and DHEAS levels in males and FSH, LH, estrogen, and DHEAS in females. The results of the study establish the effectiveness of natural products in improving fertility issues in either sex.

Hepatoprotective effects of ethanolic extract of Boerhaavia diffusa against oxaliplatin induced hepatotoxicity in albino rats.

The hepatoprotective effects of Boerhaavia diffusa was studied against the hepatotoxicity induced by oxaliplatin. Male Wistar rats were divided in three groups.Group N* control group (0.9% normal saline), Group NP0 oxaliplatin treated group and Group NP2 were prophylactically treated with Boerhaavia diffusa and then with oxaliplatin in order to assess the protective effects of Boerhaavia diffusa against the toxicity of oxaliplatin. The levels of liver enzymes ALT, AST and γ-GT were significantly reduced in the group prophylactically treated with Boerhaavia diffusa (NP2) compared with the group treated with oxaliplatin (NP0). Boerhaavia diffusa was effective in reducing risk of hypercholestremia associated with oxaliplatin. Histopathological examination of rat liver revealed that prophylactically treated group with Boerhaavia diffusa was effective in reducing oxidative stress induced steatohepatitis by oxaliplatin.