Ethanol extract of the mushroom Coprinus comatus exhibits antidiabetic and antioxidant activities in streptozotocin-induced diabetic rats

ContextEdible mushrooms have a long history of use in traditional Chinese or Japanese medicine. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) contains antioxidant and antidiabetic agents.ObjectiveTo identify the benefits of ethanol extracts of the C. comatus fruit body in streptozotocin-induced hyperglycaemic rats by evaluating their blood glucose, glycosylated haemoglobin (HbA1c), insulin, glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), and glutathione (GSH) levels, with and without extract administration.Materials and methodsWistar rats were either left untreated or were administered 45 mg/kg body weight (BW) streptozotocin; 45 mg/kg BW metformin; or 250, 500, or 750 mg/kg BW extract for 14 days. The blood glucose, GLP-1, DPP-4, GSH, insulin, and HbA1c levels were determined. Data were analysed using analysis of variance and Duncan’s multiple range tests.ResultsPreliminary data showed that administration of C. comatus ethanol extract dose of 250, 500, and 750 mg orally has no toxicity effects after 24 h administration. The ethanolic extract of fruiting body of C. comatus considerably reduced the rat’s fasting blood glucose levels 26.69%, and DPP-4 6.97% at dose of 750 mg. The extract reduced HbA1c 4–4.30%, increased GLP-1 71.09%, GSH 11.19% at dose of 500 mg, and increased insulin levels 13.83%. Extracts contain bioactive compounds such as flavonoid, alkaloid, terpenoids, vitamins C and E, rutin, and saponin.ConclusionsThe C. comatus extract can be used as herbal medicine that reduces diabetic symptoms. Further investigation on C. comatus extracts should be conducted with gas chromatography-mass spectrometry to characterise the bioactive compounds.     

D-004, a lipid extract from royal palm fruit, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice

D-004, a lipid extract of Roystonea regia fruits, has been shown to reduce Testosterone, but not dihydrotestosterone-induced prostate hyperplasia in rodents. Inhibition of prostate 5α-reductase seems to explain these effects of D-004. Finasteride, an inhibitor of 5α-reductase used to treat benign prostate hyperplasia (BPH), has been shown to produce drug-induced depression and to increase mouse immobility in the forced swim test (FST). In this study, therefore, we investigated the effect of D-004 on the immobility in the FST and the tail suspension test (TST) in mice. Also, its effects on other behavioural tests (grip strength, open field activity and rotarod test) were investigated. Mice were randomized into five groups: three groups orally treated with D-004 (250, 500 and 1000 mg/kg) or vehicle (control group), and a fifth group that received intraperitoneally (IP) imipramine 20 mg/kg for 30 days. In the FST, D-004 (250, 500 and 1000 mg/kg) produced a statistically significant reduction in immobility (51, 58, and 65%, respectively, versus the control group), whereas imipramine reduced FST immobility by 69%. In the TST, D-004 (250 and 500 mg/kg) significantly, but modestly (21%) reduced the immobility versus the control group, although less than imipramine (50%). The lowest dose of D-004 (50 mg/kg), however, was ineffective. D-004 did not alter the results of other behavioural tests. In conclusion, D-004 (250-1000 mg/kg) administered orally for 30 days reduced the immobility in the FST and the TST in mice, and had no effect on other behavioural tests in mice.     

The anti-depressant effects of a novel PDE4 inhibitor derived from resveratrol

ContextResveratrol has shown anti-stress and anti-depressant-like abilities involved in inhibiting phosphodiesterase-4 (PDE4) enzyme. However, its application is limited due to its low efficacy, bioavailability and selectivity.ObjectiveThis study synthesized a new resveratrol derivative RES003 and evaluated its PDE4 inhibitory and anti-depressant-like activities in vitro and in vivo, respectively.Materials and methodsPDEs inhibitory activities were evaluated by radioactive tracer method. Anti-depressant-like activities of novel resveratrol analogue (RES003) at doses of 2.5, 5.0 and 10 mg/kg was investigated by sugar water consumption and forced swimming tests using male ICR mice under chronic unpredictable stress procedure for 10 days. A total of 84 mice were randomly distributed into seven groups (n = 12). Drugs and vehicle were administered (intra-gastric or intra-peritoneal) once a day from the first to the last day. The molecular mechanisms were identified by western blot.ResultsRES003 showed more potent PDE4 inhibitory activity (half maximal inhibitory concentration (IC₅₀), 0.87 μM) and better selectivity than resveratrol (IC₅₀, 18.8 μM). RES003 could significantly increase the consumption of sugar water (p < 0.01) and immobility time (p < 0.01) compared to vehicle-treated stressed groups at doses of 5 and 10 mg/kg. Furthermore, RES003 could significantly increase the levels of cyclic adenosine monophosphate response element binding protein phosphorylation (10 mg/kg, p < 0.05) and brain-derived neurotrophic factor (BDNF) expression (5 and 10 mg/kg, p < 0.05 and 0.01) in mouse brain.Discussion and conclusionsRES003 could ameliorate chronic stress induced depression-like behaviours through inhibition of PDE4 and activation of cAMP-triggered phosphorylation of cAMP response element binding protein/BDNF signalling pathway. Consequently, RES003 is a promising lead compound for the treatment of depression.     

Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress,endoplasmic reticulum stress and apoptosis

ContextGentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use.ObjectiveThe present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats.Materials and methodsMale Sprague-Dawley rats (n = 3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300 mg/kg/day) and CUR (200 mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated.ResultsPre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment.Discussion and conclusionsOur findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.     

Comparison of chemical profiles,antioxidation, inhibition of skin extracellular matrix degradation,and anti-tyrosinase activity between mycelium and fruiting body of Cordyceps militaris and Isaria tenuipes

ContextCordyceps militaris and Isaria tenuipes (Cordycipitaceae) are high-value fungi that are used for health-promoting food supplements. Since laboratory cultivation has begun for these fungi, increased output has been achieved.ObjectiveThis study compared the chemical profiles, antioxidant, anti-tyrosinase, and skin extracellular matrix degradation inhibition between mycelium and fruiting body of C. militaris and I. tenuipes.Materials and methodsThe antioxidative potential of 10% v/v aqueous infused extract from each fungus was separately investigated using 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant ability, and ferric thiocyanate methods. The inhibition against MMP-1, elastase, and hyaluronidase were determined to reveal their anti-wrinkle potential. Anti-tyrosinase activities were determined.ResultsC. militaris and I. tenuipes extracts were found to contain a wide range of bioactive compounds, including phenolics, flavonoids, and adenosine. A correlation was discovered between the chemical compositions and their biological activities. The extract from I. tenuipes fruiting body (IF) was highlighted as an extraordinary elastase inhibitor (IC₅₀ = 0.006 ± 0.004 mg/mL), hyaluronidase inhibitor (IC₅₀: 30.3 ± 3.2 mg/mL), and antioxidant via radical scavenging (ABTS IC₅₀: 0.22 ± 0.02 mg/mL; DPPH IC₅₀: 0.05 ± 0.02 mg/mL), thereby reducing ability (EC₁: 95.3 ± 4.8 mM FeSO₄/g extract) and lipid peroxidation prevention (IC₅₀: 0.40 ± 0.11 mg/mL). IF had a three-times higher EC₁ value than ascorbic acid and significantly higher elastase inhibition than epigallocatechin gallate.Discussion and conclusionsIF is proposed as a powerful natural extract with antioxidant and anti-wrinkle properties; therefore, it is suggested for further use in pharmaceutical, cosmeceutical, and nutraceutical industries.     

Chrysanthemi Flos extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis

ContextAcetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. Bianliang ziyu, a variety of Chrysanthemum morifolium Ramat. (Asteraceae), has potential hepatoprotective effect. However, the mechanism is not clear yet.ObjectiveTo investigate the hepatoprotective activity and mechanism of Bianliang ziyu flower ethanol extract (BZE) on APAP-induced rats based on network pharmacology.Materials and methodsPotential pathways of BZE were predicted by network pharmacology. Male Sprague-Dawley rats were pre-treated with BZE (110, 220 and 440 mg/kg, i.g.) for eight days, and then APAP (800 mg/kg, i.g.) was used to induce liver injury. After 24 h, serum and liver were collected for biochemical detection and western blot measurement.ResultsNetwork pharmacology indicated that liver-protective effect of BZE was associated with its antioxidant and anti-apoptotic efficacy. APAP-induced liver pathological change was alleviated, and elevated serum AST and ALT were reduced by BZE (440 mg/kg) (from 66.45 to 22.64 U/L and from 59.59 to 17.49 U/L, respectively). BZE (440 mg/kg) reduced the ROS to 65.50%, and upregulated SOD and GSH by 212.92% and 175.38%, respectively. In addition, BZE (440 mg/kg) increased levels of p-AMPK, p-GSK3β, HO-1 and NQO1, ranging from 1.66- to 10.29-fold compared to APAP group, and promoted nuclear translocation of Nrf2. BZE also inhibited apoptosis induced by APAP through the PI3K–Akt pathway and restored the ability of mitochondrial biogenesis.Discussion and conclusionsOur study demonstrated that BZE protected rats from APAP-induced liver injury through antioxidant and anti-apoptotic pathways, suggesting BZE could be further developed as a potential liver-protecting agent.     

Anti-inflammatory,expectorant, and antitussive properties of Kyeongok-go in ICR mice

ContextKyeongok-go (KOG) is a traditional mixed herb preparation consisting of Panax ginseng CA Meyer (Araliaceae), Poria cocos Wolf (Polyporaceae), Rehmannia glutinosa (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated.ObjectiveThe anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases.Materials and methodsKOG (100, 200, and 400 mg/kg) was orally administered to ICR mice (n = 8) once a day for 11 days. Anti-inflammatory effects of vehicle, xylene, KOG and DEXA (1 mg/kg) were determined by monitoring edoema and redness of treated ears, and measuring the relative and absolute weight of each ear. Expectorant properties of vehicle, KOG and AM (250 mg/kg) were evaluated by observing body surface redness, and the amount of mucous secreted by the trachea. The antitussive potential of vehicle, NH₄OH, KOG and TB (50 mg/kg) was evaluated by monitoring changes in the number of coughs (for 6 min).ResultsKOG (400 mg/kg) treated mice showed 31.29% and 30.72% (p < 0.01) decreases in the relative and absolute weights of each ear relative to xylene control mice, 39.06% increases (p < 0.01) in TLF OD values relative to intact vehicle control mice, and 59.53% decrease (p < 0.01) in coughing compared to NH₄OH control mice. Dose-dependent changes were observed in all experimental models.ConclusionsKOG may be a potential therapeutic agent for the treatment of various respiratory diseases, particularly those caused by environmental toxins.     

Delphinidin-3-O-glucoside,an active compound of Hibiscus sabdariffa calyces,inhibits oxidative stress and inflammation in rabbits with atherosclerosis

ContextDelphinidin-3-O-glucoside (DP) is a bioactive compound of Hibiscus sabdariffa L. (Malvaceae) (Roselle) calyces and exerts endothelial protection and lipid-lowering activities, which provided a basis for the prevention and treatment of cardiovascular diseases.ObjectivesTo investigate the therapeutic effects of DP against atherosclerosis.Materials and methodsA rabbit model of atherosclerosis (AS) was established by 12 weeks of a high-fat diet (HFD). The rabbits were divided into five groups: control, AS, simvastatin (4 mg/kg), and two DP groups (10 and 20 mg/kg). After treatment with DP or simvastatin by oral gavage for 12 weeks, the lipid profiles were measured. Histopathological assessment of the aorta was performed by H&E staining. Oxidative stress and inflammation-related markers were analyzed by ELISA kit and real-time RT-PCR.ResultsDP (20 mg/kg) decreased serum TG (2.36 ± 0.66 vs. 4.33 ± 0.27 mmol/L for the AS group), TC, LDL-C, and HDL-C (all p < 0.05). DP (20 mg/kg) also reduced lipid levels in the liver and aorta. DP (20 mg/kg) down-regulated the mRNA levels of IL-6, VCAM-1, and NF-κB and up-regulated the mRNA levels of GSH-PX and SOD1.ConclusionsThis study proved that DP alleviated the HFD-induced oxidative stress and inflammation in atherosclerosis rabbits. These results provided the scientific basis for developing novel therapies.     

Gynura procumbens ethanol extract improves vascular dysfunction by suppressing inflammation in postmenopausal rats fed a high-fat diet

ContextGynura procumbens (Lour.) Merr. (Asteraceae) has been reported to have various pharmacological activities including anti-inflammatory effects.ObjectiveThis study sought to determine whether Gynura procumbens (GP) could improve vascular reactivity by suppressing inflammation in postmenopausal rats fed with five-times heated palm oil (5HPO) diet.Materials and methodsForty-eight female Sprague-Dawley rats were randomly divided into sham [non-ovariectomized; grouped as control, GP extracts (250 and 500 mg/kg), atorvastatin (ATV, 10 mg/kg)] and postmenopausal (PM) groups [ovariectomized rats fed with 5HPO; grouped as PM, GP extracts (250 and 500 mg/kg) and ATV (10 mg/kg)]. Each group (n = 6) was either supplemented with GP extract or ATV orally once daily for 6 months.ResultsIn comparison with the untreated PM group, 250 and 500 mg/kg GP supplementation to PM groups reduced the systolic blood pressure (103 ± 2.7, 86 ± 2.4 vs. 156 ± 7.83 mmHg, p < 0.05), intima-media thickness (101.28 ± 3.4, 93.91 ± 2.93 vs. 143.78 ± 3.31 µM), vasoconstriction percentage induced by phenylephrine (102.5%, 88.3%, vs. 51.8%), sICAM-1 (0.49, 0.26 vs. 0.56 pg/mL) and sVCAM-1 (0.39, 0.25 vs. 0.45 pg/mL). GP extract supplementation increased vasorelaxation percentage induced by acetylcholine (78.4% vs. 47.3%) and sodium nitroprusside (84.2% vs. 53.7%), increased changes in plasma nitric oxide level (1.25%, 1.31% vs. 1.9%), and suppressed the elevation of TNF-α (0.39 vs. 1.02 pg/mL), IL-6 (0.43 vs. 0.77 pg/mL) and CRP (0.29 vs. 0.69 ng/mL) in the PM groups.ConclusionsGP extract might improve vascular dysfunction by suppressing the inflammatory response, consequently preventing blood pressure elevation.     

The attenuation effect of low piperine Piper nigrum extract on doxorubicin-induced toxicity of blood chemical and immunological properties in mammary tumour rats

ContextMany natural extracts have been shown to minimize the toxicity of doxorubicin (Dox). Low piperine Piper nigrum L. (Piperaceae) extract (PFPE) is a natural extract containing many types of antioxidants that may reduce Dox toxicities.ObjectiveTo evaluate the effect of PFPE in attenuating the side effects of Dox.Materials and methodsTumour-bearing Sprague Dawley rats were divided into five groups including normal, vehicle, 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P100 + Dox), 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P200 + Dox) and Dox. Rats were treated with Dox and/or PFPE three times/week for 4 weeks. Tumour burden, blood parameters, weight of internal organs and immunological data were investigated.ResultsThe addition of 200 mg/kg PFPE significantly restored the levels of AST from 174.60 ± 45.67 U/L in the Dox group near to normal levels at 109.80 ± 4.99 U/L. The combination of PFPE and Dox also decreased the levels of CXCL7, TIMP-1, sICAM-1 and l-selectin about 1.4–1.6-fold compared to Dox group. Feeding rats with 200 mg/kg BW of PFPE combination with Dox slightly increased Th1 from 161.67 ± 14.28 cells in Dox group to 200.75 ± 5.8 cells meanwhile suppressed Treg from 3088 ± 78 cells in Dox to 2561 ± 71 cells.Discussion and conclusionsThis study showed that PFPE ameliorated Dox toxicity in many aspects indicating the role of antioxidant and other substances in the extract on toxicity attenuation. This suggested the using of PFPE may be valuable for Dox treated patients.     

2,4,6-Trihydroxy-3-geranyl acetophenone suppresses vascular leakage and leukocyte infiltration in lipopolysaccharide-induced endotoxemic mice

ContextLipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro.ObjectiveThis study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice.Materials and methodsBALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively.ResultstHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC₅₀=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC₅₀=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction.Discussion and conclusionstHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents.     

Ocimum sanctum,Zingiber officinale,and Piper nigrum extracts and their effects on gut microbiota modulations (prebiotic potential), basal inflammatory markers and lipid levels: oral supplementation study in healthy rats

ContextOcimum sanctum Linn (Labiatae) (OS), Zingiber officinale Rose (Zingiberaceae) (ZO), and Piper nigrum Linn (Piperaceae) (PN) are used in traditional medicine as immunomodulator, anti-inflammatory, and bioavailability enhancer agents.ObjectiveActive phytoconstituents of OS, ZO, PN hydro-alcoholic extracts and their effects on gut microbiota, basal inflammation and lipid profile were investigated in rats.Materials and methodsActive phytoconstituents of extracts were analysed using HPLC and GC-MS. SD rats were supplemented with individual/combined extracts (OS-850; ZO-500; PN-100 mg/kg Bw) and Fructooligosaccharide (standard prebiotic-5g/kg-Bw), orally for 30 days. Haematology, lipid profile, LPS, CRP, IL-6, insulin and histology of vital organs were analysed. Caecal bacterial levels were assessed by RT-PCR.ResultsHigh content of phenolic compounds luteolin-7-O-glucoside (430 ± 2.3 mg/100g), gallic acid (84.13 ± 1.2 mg/100 g) and flavones (88.18 ± 1.8 mg/100 g) were found in OS, ZO, and PN, respectively. Combined extract was rich in luteolin-7-O-glucoside (266.0 ± 1.80 mg/100 g). Essential oils including methyleugenol (13.96%), 6-shogaol (11.00%), piperine (18.26%), and cyclopentasiloxane (10.06%) were higher in OS, ZO, PN and combined extract. Higher levels of caecal Lactobacillus (1.7–3.4-fold), Bifidobacterium (5.89-28.4-fold), and lower levels of Firmicutes (0.04–0.91-fold), Bacteroides (0.69–0.88-fold) were noted among extracts and FOS supplemented rats. Significant (p < 0.05) decrease in plasma lipid profile and LPS was noted in all supplemented rats.Discussion and conclusionsThe current study could be first of its kind in exploring prebiotic potential of OS, ZO, PN and their effect on native gut bacterial population.     

Effects of garden cress,fenugreek and black seed on the pharmacodynamics of metoprolol: an herb-drug interaction study in rats with hypertension

ContextGarden cress (GC), fenugreek (FG), and black seed (BS) are traditional herbal medicine for managing hypertension.ObjectiveThe effects of the three herbs on the pharmacodynamics of metoprolol tartrate (MT) in hypertensive rats were investigated.Materials and methodsWistar rats were divided in five groups (n = 6). Group I served as normal control group and Group II (hypertensive control group) had rats treated orally with N-nitro L-arginine methyl ester (L-NAME, 40 mg/kg/day) only. Groups III, IV, and V rats were orally treated with L-NAME (40 mg/kg/day) + GC (300 mg/kg, once daily), L-NAME (40 mg/kg/day) + FG (300 mg/kg, once daily) and L-NAME (40 mg/kg/day) + BS (300 mg/kg, once daily), respectively, for 2 weeks, and on the 14th day, blood pressure and heart rate were recorded using a tail-cuff blood pressure-measuring system. On the 16th day, a single dose of MT (10 mg/kg) was orally administered, and the rats’ blood pressure and heart rate were recorded.ResultsGC, FG, and BS decreased systolic blood pressure (SBP) by 8.7%, 8.5%, and 8.7%, respectively, in hypertensive rats. A greater decrease in SBP by 14.5%, 14.8%, and 16.1% was observed when hypertensive rats were treated with L-NAME + GC + MT, L-NAME + FG + MT, and L-NAME + BS + MT, respectively. Similarly, hypertensive rats treated with the combination of herbs and MT had significantly lower diastolic blood pressure (DBP) than those treated with herbs alone and those treated with L-NAME alone.ConclusionsThe combination of investigated herbs and MT had a beneficial effect on hypertension. However, the concurrent administration of drugs, particularly those predominantly cleared through CYP450 2D6-catalyzed metabolism, with the three investigated herbs should be considered with caution.     

Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects

ContextStreblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.ObjectiveThe study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper.Materials and methodsAntidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay.ResultsMethanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC₅₀ values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC₅₀ values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively.Discussion and conclusionsThe methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.     

Effects of IMOD? and Angipars? on mouse D-galactose-induced model of aging

The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model. Aging was induced by D-galactose (500 mg/kg) administered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg) for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day] intraperitoneally for 4 weeks); IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks), Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks); and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α), interlukine-1β (IL-β), interlukine-6 (IL-6), Nuclear Factor-kappaB (NF-κb), total antioxidant power (TAP), lipid peroxides (LPO) and male sex hormones i.e. testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.     

Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway

ContextChinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice.ObjectiveOur study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice.Materials and methodsMale C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin–eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines.ResultsCompared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p < 0.05). 16S rDNA identification showed HQD regulated the balance of intestinal flora. Moreover, HQD suppressed the expression of RegIIIγ (p < 0.05) and prevented colonic bacterial infiltration. Furthermore, WB results showed NOD2, and TLR4 were inhibited by HQD, especially NOD2 (p < 0.01). The data of WB, qPCR, and IHC demonstrated that the NOD2-dependent pathway was inhibited by HQD (p < 0.01).Discussion and conclusionsHQD (1000 mg/kg) regulates the intestinal flora of colitis mice, mainly characterized as inhibition of the NOD2-dependent pathway. These results indicate that HQD has potential.     

Sperm quality and testicular histopathology of Wistar albino male rats treated with hydroethanolic extract of Cordia dichotoma fruits

ContextCordia dichotoma Forst. (Boraginaceae) has potent pharmacological impact. Meanwhile, its effect on fertility is unclear.ObjectiveThis study investigates the effect of Cordia fresh fruits hydroethanolic extract on fertility.Materials and methods120 Wistar albino male rats were divided into four groups (n = 30). The first group was negative control, and the second, third, and fourth groups received 125, 250, and 500 mg extract/kg bodyweight for 56 days. After 56 days, Cordia force-feeding stopped, and all groups were kept under laboratory conditions for another month to study the recovering effect.ResultsAfter day 56, extract at 500 mg/kg significantly reduced sperm total count, motility%, and alive%, to 47.60 ± 2.27 × 10⁶ sperm/mL, 43.33% ± 1.49, and 63.67% ± 1.19, respectively, abnormalities% increased considerably (26.67% ± 0.54), compared to the negative control. Also, significant depletion on follicle-stimulating hormone (2.66 ± 0.21 mIU/L), luteinizing hormone (1.07 ± 0.06 mIU/L), and testosterone (2.69 ± 0.13 nmol/L) level was recorded, compared to the negative control. Cordia negative effect showed on histopathological studies of testes, prostate, and seminal vesicles. Fortunately, these adverse effects of Cordia recovered remarkably after stopping administration for one month.ConclusionsCordia antifertility effect may be due to its hypocholesterolemic effect, where cholesterol, the steroid cycle precursor, was significantly reduced. This study can be incorporated in clinical research after being repeated on another small experimental animal, their offspring, and one large experimental animal, then going to a clinical study that we plan to do in the future.     

Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling

ContextSepsis is a systemic inflammatory disease; pristimerin exhibits strong antibacterial, anti-inflammatory and antioxidant properties.ObjectivesWe explored whether pristimerin protected against cognitive dysfunction and neuroinflammation in C57BL/6 J mice with sepsis-induced brain injuries.Materials and methodsSepsis was induced by intraperitoneal administration of 2 mg/kg lipopolysaccharide (LPS). C57BL/6 J mice were separated into four groups (n = 10 per group): positive control, negative control, pristimerin 10 mg/kg and pristimerin 100 mg/kg. Pristimerin was administered orally for 28 days prior to LPS administration and for six days thereafter. Behavioural changes were assessed one day after LPS administration using the Morris water maze and via neurological dysfunction scoring. Molecular pathogenesis was explored by measurement of malondialdehyde, superoxide dismutase, reactive oxygen species and inflammatory cytokine levels in mouse brains. Neuronal apoptosis was evaluated using the TUNEL assay. The levels of p-Akt/Akt, p-PI3K/PI3K, mTOR, Bax, Bcl-2 and caspase-3 proteins were determined via Western blotting.ResultsPristimerin improved cognitive function and reduces the neurological score to 1.15 ± 0.03. Pristimerin significantly reduced all cytokine levels: TNF-α by 18 ± 0.6 pg/mg, IL-1β by 43 ± 1.3 pg/mg and IL-6 by 34 ± 1.12 pg/mg. There was significant (p < 0.01) improvement in PI3K/Akt signalling and histopathological changes in the brain tissue of sepsis induced brain injured rats.ConclusionsPristimerin ameliorated neuronal injury by regulating PI3K/Akt signalling in mice with sepsis-induced brain injuries. Pristimerin may merit further development for clinical applications.     

Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation

ContextAtherosclerosis predisposes individuals to adverse cardiovascular events. Clinacanthus nutans L. (Acanthaceae) is a traditional remedy used for diabetes and inflammatory conditions.ObjectivesTo investigate the anti-atherosclerotic activity of a C. nutans leaf methanol extract (CNME) in a type 2 diabetic (T2D) rat model induced by a high-fat diet (HFD) and low-dose streptozotocin.Materials and methodsSixty male Sprague-Dawley rats were divided into five groups: non-diabetic fed a standard diet (C), C + CNME (500 mg/kg, orally), diabetic fed an HFD (DM), DM + CNME (500 mg/kg), and DM + Metformin (DM + Met; 300 mg/kg). Treatment with oral CNME and metformin was administered for 4 weeks. Fasting blood glucose (FBG), serum lipid profile, atherogenic index (AI), aortic tissue superoxide dismutase levels (SOD), malondialdehyde (MDA), and tumour necrosis factor-alpha (TNF-α) were measured. The rats’ aortas were stained for histological analysis and intima-media thickness (IMT), a marker of subclinical atherosclerosis.ResultsThe CNME-treated diabetic rats had reduced serum total cholesterol (43.74%; p = 0.0031), triglycerides (80.91%; p = 0.0003), low-density lipoprotein cholesterol (56.64%; p = 0.0008), AI (51.32%; p < 0.0001), MDA (60.74%; p = 0.0026), TNF-α (61.78%; p = 0.0002), and IMT (39.35%; p < 0.0001) compared to untreated diabetic rats. SOD level, however, increased (53.36%; p = 0.0326). These CNME effects were comparable to those in the metformin-treated diabetic rats.ConclusionsC. nutans possesses anti-atherosclerotic properties, which may be due to reductions in vascular tissue oxidative stress, inflammation, and serum AI. Continued studies on atherosclerotic animal models are suggested.     

Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism

ContextMoringa oleifera Lam. (Moringaceae) (MO) is an important food plant that has high nutritional and medical value. However, there is limited information on whether its seeds can improve sleep.ObjectiveThis study investigated the effects of MO seed ethanol extracts (EEMOS) on sleep activity improvement and examined the underlying mechanisms.Materials and methodsMale ICR mice were placed into six groups (n = 12) and treated as follows: Control (sodium carboxymethyl cellulose, 20 mL/kg), estazolam tablets (2 mg/kg), EEMOS (1, 2 g/kg) and kaempferol (1, 2 mg/kg). These samples were successively given intragastric for 14 d. Locomotor activity assay, pentobarbital-induced sleeping and pentetrazol-induced seizures tests were utilized to examine the sedative-hypnotic effects (SHE) of EEMOS.ResultsCompared with the control group, the results revealed that EEMOS (2 g/kg) and KA (2 mg/kg) possessed good SHE and could significantly elevate the levels of γ-aminobutyric acid and reduce the levels of glutamic acid in the mouse hypothalamus (p < 0.05). Moreover, SHE was blocked by picrotoxin, flumazenil and bicuculline (p < 0.05). EEMOS (2 g/kg) and KA (2 mg/kg) significantly upregulated the protein expression levels of glutamic acid decarboxylase-65 (GAD₆₅) and α₁-subunit of GABA_A receptors in the hypothalamus of mice (p < 0.05), not affecting glutamic acid decarboxylase-67 (GAD₆₇) and γ₂-subunit expression levels (p > 0.05). Additionally, they cause a significant increase in Cl^- influx in human cerebellar granule cells at a concentration of 8 µg/mL (p  <  0.05).Discussion and conclusionsThese findings demonstrated that EEMOS could improve sleep by regulating GABA_A-ergic systems, and encourage further clinical trials to treat insomnia.