Untargeted metabolomics, optimization of microwave-assisted extraction using Box-Behnken design and evaluation of antioxidant, and antidiabetic activities of sugarcane bagasse.

INTRODUCTION: The fruit wastes, in particular agricultural wastes, are considered potential and inexpensive sources of bioactive compounds. OBJECTIVE: The current study was aimed at the preparation of an optimized extract of sugarcane bagasse using microwave-assisted extraction (MAE) technology and comparative evaluation of chemical composition, antioxidant, and antidiabetic activities with extract prepared through maceration technique. METHODOLOGY: Box-Behnken Design (BDD) with response surface methodology was applied to observe interactions of three independent variables (ethanol concentrations [%], microwave power [W], and extraction time [min]) on the dependent variables (total phenolic content [TPC] and antioxidant status via 2,2-diphenyl-1-picrylhydrazyl [DPPH] to establish optimal extraction conditions. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis was applied for untargeted metabolite profiling, and in vitro assays were used for evaluation of the antidiabetic and antioxidant potential of the extract. Moreover, an in silico study was used to predict the interaction of five dominant compounds from the UHPLC-Q-TOF-MS profile against the dipeptidyl peptidase-IV (DPP-IV) enzyme. RESULTS: The optimal conditions for the extraction were established at 60% (v/v) ethanol, 500 W microwave power, and 5 min time with TPC 12.83 ± 0.66 mg GAE/g d.w. and DPPH 45.09 ± 0.07%. The UHPLC-Q-TOF-MS analysis revealed the presence of a total of 106 compounds in the extract. Moreover, the extract prepared through MAE technology presented higher TPC and DPPH findings than the extract prepared through maceration. Similarly, the extract was also found with good antidiabetic activity by inhibiting the DPP-IV enzyme which was also rectified theoretically by a molecular docking study. CONCLUSION: The current study presents a sustainable and an optimized approach for the preparation of sugarcane bagasse extract with functional phytoconstituents and higher antidiabetic and antioxidant activities.

Resveratrol-induced SIRT1 activation inhibits glycolysis-fueled angiogenesis under rheumatoid arthritis conditions independent of HIF-1α.

OBJECTIVE: This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. METHODS: HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. RESULTS: Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. CONCLUSION: Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation.

Phytochemical Composition and Antioxidant and Anti-Inflammatory Activities of Humboldtia sanjappae Sasidh. & Sujanapal, an Endemic Medicinal Plant to the Western Ghats.

Ethnomedicinal plants are important sources of drug candidates, and many of these plants, especially in the Western Ghats, are underexplored. Humboldtia, a genus within the Fabaceae family, thrives in the biodiversity of the Western Ghats, Kerala, India, and holds significant ethnobotanical importance. However, many Humboldtia species remain understudied in terms of their biological efficacy, while some lack scientific validation for their traditional uses. However, Humboldtia sanjappae, an underexplored plant, was investigated for the phytochemical composition of the plant, and its antioxidant, enzyme-inhibitory, anti-inflammatory, and antibacterial activities were assessed. The LC-MS analysis indicated the presence of several bioactive substances, such as Naringenin, Luteolin, and Pomiferin. The results revealed that the ethanol extract of H. sanjappae exhibited significant in vitro DPPH scavenging activity (6.53 ± 1.49 µg/mL). Additionally, it demonstrated noteworthy FRAP (Ferric Reducing Antioxidant Power) activity (8.46 ± 1.38 µg/mL). Moreover, the ethanol extract of H. sanjappae exhibited notable efficacy in inhibiting the activities of α-amylase (47.60 ± 0.19µg/mL) and ß-glucosidase (32.09 ± 0.54 µg/mL). The pre-treatment with the extract decreased the LPS-stimulated release of cytokines in the Raw 264.7 macrophages, demonstrating the anti-inflammatory potential. Further, the antibacterial properties were also evident in both Gram-positive and Gram-negative bacteria. The observed high zone of inhibition in the disc diffusion assay and MIC values were also promising. H. sanjappae displays significant anti-inflammatory, antioxidant, antidiabetic, and antibacterial properties, likely attributable to its rich composition of various biological compounds such as Naringenin, Luteolin, Epicatechin, Maritemin, and Pomiferin. Serving as a promising reservoir of these beneficial molecules, the potential of H. sanjappae as a valuable source for bioactive ingredients within the realms of nutraceutical and pharmaceutical industries is underscored, showcasing its potential for diverse applications.

The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication in the Treatment of Rheumatic Diseases.

Rheumatoid arthritis (RA) is one of the most common autoimmune disease and until now, the etiology and pathogenesis of RA is not fully understood, although dysregulation of immune cells is one of the leading cause of RA-related pathological changes. Based on current understanding, the priority of anti-rheumatic treatments is to restore immune homeostasis. There are several anti-rheumatic drugs with immunomodulatory effects available nowadays, but most of them have obvious safety or efficacy shortcomings. Therefore, the development of novel anti-rheumatic drugs is still in urgently needed. Cholinergic anti-inflammatory pathway (CAP) has been identified as an important aspect of the so-called neuro-immune regulation feedback, and the interaction between acetylcholine and alpha 7 nicotinic acetylcholine receptor (α7nAChR) serves as the foundation for this signaling. Consistent to its immunomodulatory functions, α7nAChR is extensively expressed by immune cells. Accordingly, CAP activation greatly affects the differentiation and function of α7nAChR-expressing immune cells. As a result, targeting α7nAChR will bring profound therapeutic impacts on the treatment of inflammatory diseases like RA. RA is widely recognized as a CD4+ T cells-driven disease. As a major component of innate immunity, macrophages also significantly contribute to RA-related immune abnormalities. Theoretically, manipulation of CAP in immune cells is a feasible way to treat RA. In this review, we summarized the roles of different T cells and macrophages subsets in the occurrence and progression of RA, and highlighted the immune consequences of CAP activation in these cells under RA circumstances. The in-depth discussion is supposed to inspire the development of novel cell-specific CAP-targeting anti-rheumatic regimens.

Hyperoside attenuates neuroinflammation, cognitive impairment and oxidative stress via suppressing TNF-α/NF-κB/caspase-3 signaling in type 2 diabetes rats.

OBJECTIVES: Literature findings have instituted the role of hyperglycemia-induced oxidative stress and inflammation in the pathogenesis of cognitive derangement in diabetes mellitus (DM). Hyperoside (HYP) is a flavanone glycoside reported to possess diverse pharmacological benefits such as antioxidant and anti-inflammatory properties. The study explored whether HYP could mitigate DM-induced cognitive dysfunction and further elucidate on potential molecular mechanism in rats. METHODS: Streptozotocin/high-fat diet-induced diabetic rats were treated orally with HYP (50, 200 and 400 mg/kg/day) for six consecutive weeks. The blood glucose and serum insulin levels, Morris water maze test, intraperitoneal glucose tolerance test, and brain acetylcholinesterase (AChE) activity were determined. The brain expression of inflammatory nuclear factor-kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), as well as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), lipid profile and caspase-3 activity were estimated. RESULTS: DM evoked hyperlipidemia, hypoinsulinemia, cognitive dysfunction by markedly increased AChE and reduction in learning and memory capacity. Brain activities of SOD and CAT, and levels of TAC and GSH were considerably depressed, whereas levels of IL-1ß, IL-6, TNF-α, NF-κB, caspase-3 and MDA were prominently increased. Interestingly, the HYP treatment dose-dependently abrogated the altered cognitive and biochemical parameters. DISCUSSION: The results suggested that hyperoside prevents DM-induced cognitive dysfunction, neuroinflammation and oxidative stress via antioxidant, anti-inflammatory and antiapoptotic mechanisms in rats.

Protective effect of Juglanin against doxorubicin-induced cognitive impairment in rats: Effect on oxidative, inflammatory and apoptotic machineries.

Doxorubicin (DOX) is an effective anticancer drug, however, side effects such as cognitive impairment and cardiotoxicity have limited its clinical use. Juglanin (JUG) is a flavonoid with excellent antioxidant, anti-inflammatory, neuroprotective and anticancer properties. This study investigated the protective effects of JUG against DOX-induced cognitive decline, oxidative stress and inflammatory response in rats. The rats were orally administrated with JUG or JUG in combination with DOX. After treatment, the animals were subjected to series of behavioral test including Morris water maze, Y-maze and forced swimming tests. After the study, the rats were sacrificed and the level of acetylcholinesterase (AchE), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), caspase 3 and Nuclear factor kappa B (NF-кB) were assayed in the brain. Histopathological analysis was also performed on the brain of the rats. JUG significantly protected against DOX-induced cognitive impairment and depressive behaviors. In addition, JUG attenuated altered brain histopathological architecture, reduced oxido-inflammatory responses, acetylcholinesterase and caspase 3 activity in the brain of the treated rats. Collectively, the results suggested that JUG offered neuroprotection against DOX induced Chemobrain via ameliorating oxidative stress and inflammation.

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations.

Cyclophosphamide (CTX) is one of the most commonly used alkylating agents for the treatment of various cancers; however, CTX-induced nephrotoxicity is one of the most prevailing side effects of the drug. Shorea roxburghii is a plant with diverse bioactivities including antioxidant, anti-inflammatory and renoprotective effects. This study investigated the nephroprotective effect of Shorea roxburghii phenolic extract (SRPF) against CTX-induced nephrotoxicity in rats. The rats were treated with SRPF (100 and 400 mg/kg) for 5 weeks and were concomitantly administered with CTX. The results indicated that treatment with SRPF significantly decreased serum creatinine, blood urea nitrogen (BUN), uric acid as well as renal MDA, IL-6, TNF-α, IL-1ß, NF-kB and caspase-3 levels. Furthermore, SRPF augmented the activities of renal SOD, CAT, GSH and GPx. SRPF also improved renal histopathological damages caused by CTX administration. In conclusion, these results suggested that SRPF showed substantial protective effects against CTX-mediated renal toxicity via its antioxidant and anti-inflammatory effects.

Protective Effects of Chrysin against Cyclophosphamide-Induced Cardiotoxicity in Rats: A Biochemical and Histopathological Approach.

Mounting evidences have indicated that cyclophosphamide (CyC)a potent anticancer and cytotoxic agent is associated with various organ and systemic toxicities and the cytotoxic effects observed after administration of CyC still challenges its clinical use. Chrysin (Chy) is a dietary flavonoid with prevailing antioxidant and anti-inflammatory properties. This study evaluated the protective properties of Chy against CyC-induced cardiotoxicity in rats. The animals were orally treated with Chy (25 and 50 mg/kg/day) for 35 days and exposed to CyC (i. p., 100 mg/kg) once a week for four weeks. The results indicated that CyC caused significant cardiotoxicity as manifested by notable increases in heart weight, cardiac function biomarkers such as lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), troponin T and aspartate transaminase (AST). In addition, cardiac malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL1 ß) and interleukin 6 (IL-6) levels were considerably increased. Meanwhile, cardiac antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) level were suppressed, while H&E stained histopathological assessment showed marked alterations in cardiac tissues. CyC also significantly lowered red blood cells (RBC) and white blood cells (WBC) parameters, whereas treatment with Chy significantly restored the altered biochemical and histopathological features. Conclusively, aforementioned results inferred that Chy offered cardioprotective potentials against CyC-induced cardiotoxicity which may be due to its antioxidant, and anti-inflammatory properties.

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats.

In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high fructose/streptozotocin, and the diabetic rats were treated with MSE (50 and 200 mg/kg) for 5 weeks. After treatment, the animals were subjected to a forced swim test, open field test and elevated plus-maze tests. Additionally, proinflammatory cytokines and oxidative stress parameters were evaluated in the brain tissues of the rats. UPLC/ESI/TOF-MS analysis revealed that MSE is abundantly rich in polyphenolic constituents, notably flavonoid and phenolic glycosides. Behavioral tests and biochemical analyses indicated that diabetic rats showed significantly increased anxiety and depressive-like behavioral deficits, brain oxidative stress and pro-inflammatory cytokines levels (IL-1ß, IL-6 and TNF-α). Treatment with MSE (50 and 200 mg/kg) significantly attenuated increased blood glucose level, depressive and anxiety-like behaviors in diabetic rats. Additionally, the antioxidant enzymes activities were markedly increased in MSE-treated animals, while TNF-α, IL-1ß and IL-6 cytokines were notably suppressed. Taken together, these results suggested that MSE has potentials as antidepressant and anxiolytic-like effects and improves the brain oxido-inflammatory status in diabetic rats.

Antimicrobial and Larvicidal Activities of Different Ocimum Essential Oils Extracted by Ultrasound-Assisted Hydrodistillation.

Infectious diseases and their vectors have remained a concern for human population from their historical origin. Microbial pathogens have also emerged as a potent threat to the healthcare systems even in developed countries. Essential oils remain a less explored method for infectious disease control; besides, the ultrasound-assisted extraction (UAE) of essential oil production has emerged as promising source of bioactive volatiles over conventional methods. This study analyzed the possible use of UAE- Essential oils (EOs) from different species of Ocimum plants (Ocimum basilicum (OB), O. gratissimum (OG), O. tenuiflorum (OT), and O. canum (OC)) in the management of microbial pathogens and mosquito larval control. The antibacterial activity was estimated in terms of a disc diffusion assay and minimum inhibitory concentrations against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enteritidis. The larvicidal property was found using three important mosquito vectors and the LC50 value was determined. Furthermore, antioxidant and anti-inflammatory properties were estimated in terms of radical scavenging activities and the inhibition of lipoxygenase enzyme activity. The EOs exhibited significant DPPH radical scavenging (high in OG), hydrogen-peroxide scavenging (OB) and lipoxygenase inhibition (OB). The antibacterial activity was high in OB and OG (p < 0.05) and the larvicidal activity was of higher sensitivity against Aedis and Culex, whereas Armigeres was more resistant. However, no sign of toxicity in the Allium cepa model or non-targeted organism Guppy fishes was observed. Overall, the UAE extracted Ocimum essential oils were found to be effective against various human pathogenic microbial organisms, with OB and OG being highly active. Likewise, the EOs was also able to induce mortality in the larval forms of various mosquito vectors.

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis.

Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, antioxidant and antiapoptotic properties. This study evaluated the effect of COST on DXB-induced cardiorenal toxicity in rats. Rats were orally treated with COST for 4 weeks and received weekly 5 mg/kg doses of DXB for three weeks. Cardiorenal biochemical biomarkers, lipid profile, oxidative stress, inflammatory cytokines, histological and immunohistochemical analyses were evaluated. DXB-treated rats displayed significantly increased levels of lipid profiles, markers of cardiorenal dysfunction (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin T, blood urea nitrogen, uric acid and creatinine). In addition, DXB markedly upregulated cardiorenal malondialdehyde, tumor necrosis factor-α, interleukin-1ß, interleukin-6 levels and decreased glutathione, superoxide dismutase and catalase activities. COST treatment significantly attenuated the aforementioned alterations induced by DXB. Furthermore, histopathological and immunohistochemical analyses revealed that COST ameliorated the histopathological features and reduced p53 and myeloperoxidase expression in the treated rats. These results suggest that COST exhibits cardiorenal protective effects against DXB-induced injury presumably via suppression of oxidative stress, inflammation and apoptosis.

New Insights on Acanthus ebracteatus Vahl: UPLC-ESI-QTOF-MS Profile, Antioxidant, Antimicrobial and Anticancer Activities.

This study investigated the antioxidant, antimicrobial, anticancer, and phytochemical profiling of extracts from the leaves and stem/root of Acanthus ebracteatus (AE). The total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical-scavenging activity, 2, 2'-azino-Bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging activity, metal chelating activities (MCA), ferric reducing antioxidant power (FRAP) and oxygen radical antioxidant capacity (ORAC) were used for antioxidant assessment. The ethanolic extracts of the leaves (AEL-nor) and stem/root (AEWP-nor) without chlorophyll removal and those with chlorophyll removal, using sedimentation process (AEL-sed and AEWP-sed), were prepared. Generally, AEL-sed showed the highest antioxidant activity (FRAP: 1113.2 µmol TE/g; ORAC: 11.52 µmol TE/g; MCA: 47.83 µmol EDTA/g; ABTS 67.73 µmol TE/g; DPPH 498.8 µmol TE/g; TPC: 140.50 mg/GAE g and TFC: 110.40 mg/CE g) compared with other extracts. Likewise, AEL-sed also showed the highest bacteriostatic (MIC) and bactericidal (MBC) effects, as well as the highest anticancer and antiproliferative activity against oral squamous carcinoma (CLS-354/WT) cells. UPLC-ESI-QTOF/MS analysis of AEL-sed and AEWP-sed tentatively identified several bioactive compounds in the extracts, including flavonoids, phenols, iridoids, and nucleosides. Our results provide a potentially valuable application for A. ebracteatus, especially in further exploration of the plant in oxidative stress-related disorders, as well as the application of the plant as potential nutraceuticals and cosmeceuticals.

Antioxidant, Antimicrobial, Cytotoxicity, and Larvicidal Activities of Selected Synthetic Bis-Chalcones.

Plants are known to have numerous phytochemicals and other secondary metabolites with numerous pharmacological and biological properties. Among the various compounds, polyphenols, flavonoids, anthocyanins, alkaloids, and terpenoids are the predominant ones that have been explored for their biological potential. Among these, chalcones and bis-chalcones are less explored for their biological potential under in vitro experiments, cell culture models, and animal studies. In the present study, we evaluated six synthetic bis-chalcones that were different in terms of their aromatic cores, functional group substitution, and position of substitutions. The results indicated a strong antioxidant property in terms of DPPH and ABTS radical-scavenging potentials and ferric-reducing properties. In addition, compounds 1, 2, and 4 exhibited strong antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella enteritidis. The disc diffusion assay values were indicative of the antibacterial properties of these compounds. Overall, the study indicated the antioxidant and antimicrobial properties of the compounds. Our preliminary studies point to the potential of this class of compounds for further in vivo investigation.

Chemical Composition, Antioxidant, Anti-Bacterial, and Anti-Cancer Activities of Essential Oils Extracted from Citrus limetta Risso Peel Waste Remains after Commercial Use.

Citrus plants are widely utilized for edible purposes and medicinal utility throughout the world. However, because of the higher abundance of the antimicrobial compound D-Limonene, the peel waste cannot be disposed of by biogas production. Therefore, after the extraction of D-Limonene from the peel wastes, it can be easily disposed of. The D-Limonene rich essential oil from the Citrus limetta risso (CLEO) was extracted and evaluated its radical quenching, bactericidal, and cytotoxic properties. The radical quenching properties were DPPH radical scavenging (11.35 ± 0.51 µg/mL) and ABTS scavenging (10.36 ± 0.55 µg/mL). There, we observed a dose-dependent antibacterial potential for the essential oil against pathogenic bacteria. Apart from that, the essential oil also inhibited the biofilm-forming properties of E. coli, P. aeruginosa, S. enterica, and S. aureus. Further, cytotoxicity was also exhibited against estrogen receptor-positive (MCF7) cells (IC50: 47.31 ± 3.11 µg/mL) and a triple-negative (MDA-MB-237) cell (IC50: 55.11 ± 4.62 µg/mL). Upon evaluation of the mechanism of action, the toxicity was mediated through an increased level of reactive radicals of oxygen and the subsequent release of cytochrome C, indicative of mitotoxicity. Hence, the D-Limonene rich essential oil of C. limetta is useful as a strong antibacterial and cytotoxic agent; the antioxidant properties exhibited also increase its utility value.

Antinociceptive, Anti-Hyperalgesia and Antiallodynic Activities of Polyphenol Rich Extract from Shorea roxburghii against Cyclophosphamide Induced Peripheral Neuropathy.

Cyclophosphamide (CYP) is a widely used antineoplastic and immunosuppressive drug, however, despite its efficacy, it has shown extensive multiple organ toxicities, including peripheral neuropathy which significantly affects the quality of life of cancer patients. This study elucidated the protective properties of Shorea roxburghii polyphenol extract (SLPE) in CYP-induced peripheral neuropathy. Rats were treated with SLPE (100 and 400 mg/kg) for five weeks plus CYP once a week from the second week of SLPE treatment. Using UHPLC-QTOF-MS, 54 polyphenolic compounds were identified in SLPE extract. After the treatment period the antinociceptive, anti-hyperalgesia and antiallodynic effects was evaluated using formalin paw edema, acetic acid abdominal writhing, hot plate, tail immersion and von Frey filament tests. While the locomotive and motor coordination effects were evaluated by open field and rotarod tests. The administration of CYP led to significant increases in mechanical and thermal hyperalgesia, in addition to hyper-nociceptive responses in the formalin and acetic acid writhing tests. CYP also significantly reduced locomotive activity and motor coordination. SLPE significantly protected against CYP-induced mechanical and thermal hyperalgesia. Furthermore, SLPE displayed robust antinociceptive effect by counteracting formalin and acetic acid induced hyper-nociception. In addition, SLPE increased the locomotive activity as well as the grip and motor coordination of the CYP treated rats. In conclusion, these results revealed the protective effects of SLPE against CYP-induced peripheral neuropathy and could be an effective therapeutic remedy for chemotherapy induced peripheral neuropathy.

Alleviation of Liver Dysfunction, Oxidative Stress, and Inflammation Underlines the Protective Effects of Polysaccharides from Cordyceps cicadae on High Sugar/High Fat Diet-Induced Metabolic Syndrome in Rats.

This study investigated the protective effects of two polysaccharides (CPA-1 and CPB-2) from Cordyceps cicadae against high fructose/high fat diet (HF/HFD) induced obesity and metabolic disorders in rats. Rats were either fed with normal diet or HF/HFD and treated with CPA-1 and CPB-2 (100 and 300 mg/kg) for 11 weeks. Administration of CPA-1 and CPB-2 significantly and dose dependently reduced body and liver weight, insulin and glucose tolerance, serum insulin and glucose levels. Furthermore, serum and hepatic lipid profiles, liver function enzymes and proinflammatory cytokines (TNF-α, IL-1ß and IL-6) were markedly reduced. Additionally, CPA-1 and CPB-2 treatment alleviated hepatic oxidative stress by reducing lipid peroxidation level (MDA) and upregulating glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities as well as ameliorated histological alterations through the reduction of hepatic lipid accumulation. These results suggested that the polysaccharides from C. cicadae showed protective effects against HF/HFD induced metabolic disturbances and may be considered as a dietary supplement for treating obesity.

Protective effects of ethyl acetate extract from Shorea roxburghii against diabetes induced testicular damage in rats.

Diabetic mellitus is a chronic metabolic disorder that is associated with several complications including testicular dysfunction. This research investigated the protective action of the ethyl acetate extract from Shorea roxburghii (SRE) on diabetes induced testicular damage in rats. Diabetic rats were orally administered with SRE at doses of 100 and 400 mg/kg for 4 weeks. SRE improved the body weight gain, testes weight, testes index and increased serum concentration of testosterone. Furthermore, SRE increased the testicular antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase. In addition, SRE ameliorated testicular inflammatory mediators such as myeloperoxidase, tumor necrosis factor alpha, interleukin 6, p38 MAPK and nuclear factor kappa B activation and decreased testicular cell apoptosis in the treated diabetic rats. SRE also raised sperm parameters after treatment of diabetic rats. Conclusively, our results suggested that SRE ameliorated diabetes induced testicular damage by inhibiting oxidative stress and inflammation.

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro-inflammatory responses in rats.

BACKGROUND: Literature has demonstrated that diabetes is associated with renal complication and testicular dysfunctions. The current study explored the potential of Tiliacora triandra extract and its major component against diabetic kidney and testicular damages in rats. METHODS: Diabetes was induced by high fat diet/streptozotocin (HFD/STZ) and treated orally with Tiliacora triandra extract (TTE, 100 and 400 mg kg-1 body weight) and its major component, 5,7-dihydroxy-6-oxoheptadecanoic acid (DHA, 25 mg kg-1 body weight) for 30 consecutive days. Testicular activities of testicular enzymes, serum levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), sperm parameters and urinalysis for protein and albumin levels were evaluated. Renal and testicular biomarkers of oxidative stress and pro-inflammation were analysed along with histology. RESULTS: The experimental diabetes induced significant alterations in the levels and activities of indices evaluated compared to non-diabetic normal rats. The 28-day treatment of diabetic rats with TTE and DHA markedly improved activities of testicular enzymes, restored levels of testosterone, LH and FSH and sperm parameters compared to untreated diabetic rats. TTE and DHA abrogated proteinuria and reversed urine albumin level. Testicular and renal oxidative stress and pro-inflammation were attenuated in diabetic rats treated with TTE and DHA. The diabetes-mediated histopathological damage was alleviated in the kidney and testis. CONCLUSION: The protective effect of TTE and DHA against diabetes induced kidney and testicular damages may be related to its antioxidant and anti-inflammatory activities. © 2020 Society of Chemical Industry.

Shorea roxburghii Leaf Extract Ameliorates Hyperglycemia Induced Abnormalities in High Fat/Fructose and Streptozotocin Induced Diabetic Rats.

This study investigated the hypoglycemic effect of the methanol extract of Shorea roxburghii leaves (SRL) in high fat diet/high fructose solution (HFDHF) and streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) in rats as well as evaluating its ameliorative potentials in altered biochemical and hematological parameters in the treated rats. T2DM was induced in Sprague Dawley (SD) rats by feeding with HFDHF for 4 weeks and administering STZ (35 mg/kg, i. p.). Diabetic rats were given SRL extract at doses of 100 and 400 mg/kg for 30 days. The food and water intake were monitored on a daily basis, while the fasting blood glucose (FBG) levels and body weight were measured weekly. Biochemical and hematological parameters as well as histopathological studies of the pancreas were also evaluated. SRL significantly decreased FBG and improved the body weight, food and water intake of treated diabetic rats. Furthermore, biochemical and hematological parameters including liver and kidney function enzymes, lipid profiles, white blood and red blood cells parameters were markedly ameliorated by SRL. Histopathological analyses of the pancreas indicated reconstitution of ß-cells architecture in SRL treated rats. The results of this study suggest that SRL has antidiabetic potential and can be considered for the treatment of T2DM.

Protective Effects of Nucleosides-Rich Extract from Cordyceps cicadae against Cisplatin Induced Testicular Damage.

Cisplatin (CISP) is an efficacious anticancer agent used in chemotherapy, however, the constraint to its clinical utility is the stray organ toxicity including testicular damage linked to oxidative and inflammatory cascades. This study aimed to explore the protective effect of nucleosides-rich extract from Cordyceps cicadae (NRCE) against CISP-induced testicular damage in rats. Rats were subjected to prophylactic oral administration of NRCE (50, 100 and 400 mg/kg body weight/day) for 7 days prior to testicular toxicity induced by CISP (10 mg/kg, ip) and were sacrificed after 72 h post-CISP injection. Cisplatin caused significant deficits in sperm count, viability and motility, testosterone and follicle stimulating hormone (FSH) compared to normal control. It depressed testicular activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), total antioxidant content (TAC), whereas malondialdehyde (MDA) increased remarkably. CISP considerably increased tumor necrosis factor-alpha (TNF-α) and interleukin-one beta (IL-1ß) with alterations in testis histology compared to normal control. Interestingly, NRCE pretreatment inhibited the CISP-induced alterations in reproductive indices, restored the antioxidant activities in testes as well as inflammatory mediators and histology comparable to control. Our findings demonstrate that NRCE could prevent CISP testicular damage via inhibition of oxidative stress and pro-inflammation in rats.