Epigallocatechin-3-gallate counters cisplatin toxicity of rat testes

Context: Epigallocatechin-3-gallate (EG), the main active flavonoid in green tea, has well-known anti-inflammatory, antioxidant, and anti-apoptotic activities.

Objective: The EG protection against testicular injury induced by cisplatin was studied in Sprague–Dawley rats.

Materials and methods: Cisplatin (10?mg/kg, i.p) was given as a single injection to rats. EG was given at 40 and 80?mg/kg/day, i.p., for 5 days, starting the same day of cisplatin insult. Serum testosterone, and testicular malondialdehyde, total antioxidant status, nitric oxide, interleukin-6, interleukin-1β, cytochrome C, Bax/Bcl-2 ratio, and caspase-3 were measured. In addition, testicular histopathological examination and immunohistochemical expression of testicular tumour necrosis factor-α were evaluated.

Results: Cisplatin, compared to the control, significantly decreased serum testosterone (6.48?±?0.7 vs. 50.8?±?4.91?ng/10?mL), and testicular tissue antioxidant status (17.3?±?1.21 vs. 64.12?±?5.4?μmol/g), and significantly increased interleukin-6 (85.81?±?6.11 vs. 38.2?±?2.79?pg/100?mg), interleukin-1β (98.09?±?8.31 vs. 32.52?±?2.08?pg/100?mg), malondialdehyde (74.5?±?5.88 vs. 23.8?±?1.91?nmol/g), nitric oxide (104.98?±?8.5 vs. 52.68?±?5.12?nmol/100?mg), cytochrome C (5.97?±?0.33 vs. 1.6?±?0.99?ng/mg protein), Bax/Bcl-2 ratio (4.01?±?0.38 vs. 0.71?±?0.0), and caspase-3 (3.2?±?0.21 vs. 0.98?±?0.08?O.D. 405?nm) in rat testes. EG (40 and 80?mg/kg, respectively) caused significant increases of serum testosterone (33.9?±?2.89 and 47.88?±?4.4?ng/10?mL), and testicular antioxidant status (47.1?±?3.92 and 58.22?±?3.58?μmol/g), and significant decreases of interleukin-6 (57.39?±?4.2 and 48.18?±?3.98?pg/100?mg), interleukin-1β (65.12?±?5.88 and 41.96?±?3.51?pg/100?mg), malondialdehyde (42.3?±?3.9 and 28.67?±?2.49?nmol/g), nitric oxide (70.6?±?6.79 and 61.31?±?5.18?nmol/100?mg), cytochrome C (3.4?±?0.27 and 2.21?±?0.18?ng/mg protein), Bax/Bcl-2 ratio (1.49?±?0.14 and 1.1?±?0.09), and caspase-3 (2.1?±?0.17 and 1.48?±?0.13?O.D. 405?nm) in testes of cisplatin-treated rats. Additionally, both doses of EG significantly ameliorated the histopathological injury and reduced tumour necrosis factor-α expression in rat testes.

Conclusion: EG can afford testicular protection in cisplatin-challenged rats by its antioxidant, antinitrative, anti-inflammatory and antiapoptotic effects.     

Crataegus Aronia protects and reverses vascular inflammation in a high fat diet rat model by an antioxidant mechanism and modulating serum levels of oxidized low-density lipoprotein

Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.

Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.

Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.

Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.

Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.     

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice

Context: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD).

Objective: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS).

Materials and methods: Male BALB/c mice were treated with standardized myrtol for 1.5?h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively.

Results: In LPS-challenged mice, standardized myrtol at a dose of 1200?mg/kg significantly inhibited the neutrophile counts (from 820.97?±?142.44 to 280.42?±?65.45, 10³/mL), protein concentration (from 0.331?±?0.02 to 0.183?±?0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70?±?748.40 to 2317.70?±?500.14, ng/mL; IL-6: from 1184.85?±?143.58 to 509.57?±?133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82?±?0.04 to 0.48?±?0.06, U/g) and pathological changes (lung injury score: from 11.67?±?0.33 to 7.83?±?0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues.

Discussion and conclusion: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.     

Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with atorvastatin calcium (AC) for treating coronary heart disease in the clinic.

Objective: This study investigated the effects of DST on the pharmacokinetics of AC and the potential mechanism.

Materials and methods: The pharmacokinetics of AC (1?mg/kg) with or without pretreatment of DST (100?mg/kg) were investigated using LC-MS/MS. The effects of DST (50?μg/mL) on the metabolic stability of AC were also investigated using rat liver microsome incubation systems.

Results: The results indicated that C_max (23.87?±?4.27 vs. 38.94?±?5.32?ng/mL), AUC_(0–t) (41.01?±?11.32 vs. 77.28?±?12.92?ng h/mL), and t_1/2 (1.91?±?0.18 vs. 2.74?±?0.23?h) decreased significantly (p?t_1/2) of AC was also decreased (25.7?±?5.2 vs. 42.5?±?6.1) with the pretreatment of DST.

Discussion and conclusions: This study indicated that the main components in DST could accelerate the metabolism of AC in rat liver microsomes and change the pharmacokinetic behaviors of AC. So these results showed that the herb-drug interaction between DST and AC might occur when they were co-administered. Therefore, the clinical dose of AC should be adjusted when DST and AC are co-administered.     

Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice

Context: Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury.

Objective: To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice.

Materials and methods: KM mice were orally administered with alcohol (56%, 6?mL/kg) for 30?d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60?mg/kg) or GP (250 and 150?mg/kg) were given 5?h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected.

Results: In GP-H group, ALT and AST decreased to 18.85?±?4.71?U/L and 40.84?±?7.89?U/L. MDA, TC, TG and LDL-C decreased to 2.32?±?0.86?mmol/mg, 0.21?±?0.12?mmol/L, 0.96?±?0.31?mmol/L and 0.084?±?0.027?mmol/L. SOD, GSH-Px and GSH increased to 118.32?±?16.32?U/mg, 523.72?±?64.20?U/mg and 0.56?±?0.05?mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608?±?0.170 and 1.057?±?0.058, decorin increased to 2.182?±?0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment.

Discussion and conclusions: Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis.     

Mineral pitch stimulates humoral,cellular and innate immune responses in mice

Abstract

Context: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer.

Objective: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity.

Materials and methods: Mice given MP (100, 200, 300 or 400?mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function.

Results: MP increased PFC (330.2 versus 182.2/10⁶ splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400?mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470?pg/ml) and decreased IL-4 (96 versus 178?pg/ml). CD4⁺/CD3⁺ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62?±?0.59 (versus 16.47?±?0.72) and 1.59?±?0.12 (versus 0.87?±?0.10?mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14?±?0.60 versus 5.81?±?0.40 SI) and macrophage phagocyte response (0.24?±?0.02 versus 0.15?±?0.009), expressed as absorbance at 570?nm, but decreased nitrite production (17.4?±?1.10 versus 24.3?±?1.30?µM/10⁶ cells). We also observed an increased bone marrow cellularity (24.5?±?1.10 versus 17.10?±?0.70 cells/femur) and WBC count (12?667?±?377 versus 9178?±?213 cells/mm³) following MP treatment. There was no sign of toxicity at 400?mg/kg, 1/12th of reported LD₅₀.

Conclusion: MP elicits a dose-dependent Th1 immune response.     

Effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism

Context: Asiatic acid has been reported to possess a wide range of pharmacological activities.

Objective: This study investigates the effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential mechanism.

Materials and methods: The pharmacokinetics of orally administered asiatic acid (20?mg/kg) with or without glycyrrhizin pretreatment (100?mg/kg/day for seven days) were investigated using a LC–MS method. Additionally, the Caco-2 cell transwell model and rat liver microsome incubation systems were used to investigate the potential mechanism of glycyrrhizin’s effects on the pharmacokinetics of asiatic acid.

Results: The results showed that the C_max (221.33?±?21.06 vs. 324.67?±?28.64?ng/mL), AUC_0–inf (496.12?±?109.31 vs. 749.15?±?163.95?μg·h/L) and the t_1/2 (1.21?±?0.27 vs. 2.04?±?0.32?h) of asiatic acid decreased significantly (p?p?Discussion and conclusions: In conclusion, these results indicated that glycyrrhizin could decrease the system exposure of asiatic acid, possibly by inducing the activity of P-gp or CYP450 enzyme.     

Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats

Context: Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus.

Objective: This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats.

Materials and methods: Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10?mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed.

Results: This study showed that MC caused a significant reduction of serum glucose (135.99?±?6.27 and 149.79?±?1.90 vs. 253.40*?±?8.18) for prophylaxis and treatment respectively, fructosamine (0.99?±?0.01 and 1.01?±?0.04 vs. 3.04?±?0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13?±?0.08 and 1.19?±?0.05 vs. 1.48?±?1.47) and pancreatic malondialdehyde content (p?p?p?Conclusions: Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is used for prophylaxis or treatment.     

Influence of andrographolide on the pharmacokinetics of warfarin in rats

Context: Andrographolide and warfarin are often used together in clinics in China. However, the herb-drug interaction between andrographolide and warfarin is still unknown.

Objective: This study investigates the herb-drug interaction between andrographolide and warfarin in vivo and in vitro.

Materials and methods: A sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in male Sprague-Dawley rats plasma, and then the pharmacokinetics of orally administered warfarin (0.5?mg/kg) with or without andrographolide (30?mg/kg/day for 7?days) pretreatment was investigated. In addition, Sprague-Dawley rat liver microsomes incubation systems were used to support the in vivo pharmacokinetic data and investigate its potential mechanism.

Results: The method validation results showed that a sensitive and reliable LC-MS/MS method was developed for the determination of warfarin in rat plasma samples. The pharmacokinetic results indicated that co-administration of andrographolide could increase the systemic exposure of warfarin significantly, including area under the curve (118.92?±?18.08 vs. 60.58?±?9.46?μg?×?h/mL), maximum plasma concentration (3.32?±?0.41 vs. 2.35?±?0.25?μg/mL) and t_1/2 (22.73?±?3.28 vs. 14.27?±?2.67?h). Additionally, the metabolic stability of warfarin increased from 23.5?±?4.7 to 38.7?±?6.1?min with the pretreatment of andrographolide, and the difference was significant (p?Discussion and conclusion: In conclusion, andrographolide could increase the systemic exposure of warfarin in rats when andrographolide and warfarin were co-administered, and possibly by slowing down the metabolism of warfarin in rat liver by inhibiting the activity of CYP3A4 or CYP2C9.     

Antioxidant capacity of Typha angustifolia extracts and two active flavonoids

Context: The pollen of Typha angustifolia L. (Typhaceae) has been used as a traditional Chinese medicine for improving the microcirculation and promoting wound healing. Flavonoids are the main constituent in the plant, but little is known about the antioxidant activity of the principal constituent of the pollen in detail.

Objectives: To assess the antioxidant activities of ethanol and water extracts and two constituents of the pollen.

Materials and methods: Plant material (1?g) was extracted by 95% ethanol and water (10?mL?×?2, 1?h each), respectively. The extracted activities (0.8–2.6?mg/mL) were measured by DPPH and the reducing activity of ferric chloride (1.7–2.6?mg/mL). Typhaneoside and isorhamnetin-3-O-neohesperidoside (I3ON) (2.8–70?μmol/L) were investigated on the relationship between NO, MDA and SOD in HUVECs treated with 100?μg/mL of LPS for 24?h.

Results: Nine compounds were identified by UPLC-MS. Ethanol extract showed IC₅₀ values in DPPH (39.51?±?0.72) and Fe³⁺ reducing activity (82.76?±?13.38), higher than the water extract (50.85?±?0.74) and (106.33?±?6.35), respectively. Typhaneoside and I3ON promoted cell proliferation at the respective concentration range of 2.8 to 70?μmol/L (p?p?p?p?Conclusions: The constituents from Typha angustifolia could be a novel therapeutic strategy for LPS-induced inflammation.     

Rutin ameliorates oxidative stress and preserves hepatic and renal functions following exposure to cadmium and ethanol

Context: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating potentials.

Objective: This study was designed to evaluate the protective effects of RUT against cadmium (Cd)?+?ethanol (EtOH)-induced hepatic and renal toxicity in rats.

Materials and methods: Wistar rats were treated with Cd (50?mg/kg) alone or in combination with EtOH (5?mg/kg) and RUT (25, 50 and 100?mg/kg) for 15?days. After treatment, the liver, kidney and serum were removed for biochemical assays by spectrophotometric methods.

Results: Serum, hepatic and renal malondialdehyde (MDA) levels were highest in the Cd?+?EtOH group and lowest in Cd?+?EtOH animals co-treated with the highest dose of RUT (2.98?±?0.34, 10.08?±?2.32, 4.99?±?1.21 vs. 1.69?±?0.33, 6.13?±?0.28, 3.66?±?1.12?μmol MDA/mg protein, respectively). The serum level of Cd was increased in the Cd?+?EtOH treated animals compared to Cd?+?EtOH animals co-treated with 100?mg/kg RUT (2.54?±?0.08 vs. 1.28?±?0.04?ppm). Furthermore, RUT at the highest dose protected against Cd?+?EtOH-induced elevation of bilirubin and uric acid levels as well as activities of lactate dehydrogenase and γ-glutamyl transferase (62.86?±?2.74 vs. 122.52?±?6.35?µmol/L; 1.77?±?0.35 vs. 3.23?±?0.55?mmol/L; 9.56?±?1.22 vs. 16.21?±?1.64?U/L; 288.92?±?40.12 vs. 159.8?±?18.01?U/L). The histo-pathological changes in the liver and kidney were also reduced in the Cd?+?EtOH animals co-treated with RUT in a dose-dependent manner.

Discussion and conclusion: RUT protected against the combined effects of Cd?+?EtOH on hepatic and renal functions and improved the antioxidant defence system in the blood.     

The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism

Context: Combining sorafenib with triptolide could inhibit tumour growth with greater efficacy than single-agent treatment. However, their herb–drug interaction remains unknown.

Objective: This study investigates the herb–drug interaction between triptolide and sorafenib.

Materials and methods: The effects of triptolide (10?mg/kg) on the pharmacokinetics of different doses of sorafenib (20, 50 and 100?mg/kg) in rats, and blood samples were collected within 48?h and evaluated using LC-MS/MS. The effects of triptolide on the absorption and metabolism of sorafenib were also investigated using Caco-2 cell monolayer model and rat liver microsome incubation systems.

Results: The results showed that the C_max (low dose: 72.38?±?8.76 versus 49.15?±?5.46?ng/mL; medium dose: 178.65?±?21.05 versus 109.31?±?14.17?ng/mL; high dose: 332.81?±?29.38 versus 230.86?±?9.68?ng/mL) of sorafenib at different doses increased significantly with the pretreatment of triptolide, and while the oral clearance rate of sorafenib decreased. The t_1/2 of sorafenib increased significant (p?Discussion and conclusions: These results indicated that triptolide could change the pharmacokinetic profiles of sorafenib in rats; these effects might be exerted via decreasing the intrinsic clearance rate of sorafenib in rat liver.     

Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism

Context: Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia.

Objective: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint.

Materials and methods: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01–2.55?mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists.

Results: The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC₅₀ of 0.057?±?0.006 and 0.430?±?0.196?mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC₅₀ 0.971?±?0.459?mg/mL), methylene blue (EC₅₀ 1.203?±?0.426?mg/mL), indomethacin (EC₅₀ 2.128?±?1.218?mg/mL), atropine (EC₅₀ 0.470?±?0.325?mg/mL), and propranolol (EC₅₀ 0.314?±?0.032?mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC₅₀ 0.548?±?0.184, 0.158?±?0.012, 0.847?±?0.342, and 0.304?±?0.075?mg/mL, respectively). VAE was also found to be active in reducing Ca²⁺ released from the sarcoplasmic reticulum and blocking calcium channels.

Conclusions: The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI₂ signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β₂-adrenergic receptor levels.     

The protective effect of qiancao naomaitong mixture on neuronal damage and cerebral ischemia/reperfusion injury

Context Qiancao Naomaitong Mixture (QNM) is mainly used to treat ischemic stroke patients in the clinic.

Objective This study evaluates the protective effect of QNM on neuronal damage in vitro, and clarifies the underlying mechanism against cerebral ischemia-reperfusion (I/R) injury in vivo.

Materials and methods Activity assay of caspase 3 (C-3) and caspase 8 (C-8) were measured with microplate reader and cell apoptosis was investigated. Cerebral I/R injury was induced by MCAO model. QNM groups were given at 0.27, 0.54 and 1.08?mL/100?g body weight. The weight ratio of cerebral infarction tissue was obtained. The cytokine levels in serum and brain tissue were measured using ELISA.

Results Compared with the OGD group (C-3: 29.69?±?5.63, C-8: 74.05?±?6.86), 100?mg/mL QNM (C-3: 19.80?±?2.62, C-8: 48.94?±?6.41) and 200?mg/mL QNM (C-3: 16.28?±?4.55, C-8: 41.08?±?4.05) treatments decreased C-3 and C-8 activities significantly, and inhibited apoptosis of SH-SY5Y cells. The weight ratios of cerebral tissues in low, medium and high dose groups were 17.33?±?5.1%, 17.78?±?5.4% and 14.25?±?4.2%, respectively, significantly lower than in control group. QNM also improved the cytokine levels in serum and brain tissue. In addition, histological examination indicated that dense neuropil and largely surviving neurons were seen in treated rats.

Conclusion QNM exerted protective effect by inhibiting the cell apoptosis in vitro. The protective mechanisms of QNM were associated with its properties of anti-apoptosis and antioxidation as well as improved neuronal nutrition in I/R rats.     

Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber of Dioscorea alata

Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess anti-inflammatory properties in traditional medicine.

Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract.

Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48?h with six different concentrations (0–80?μg/mL) of the extract. The expression of nitric oxide (NO), TNF-α, COX-1, COX-2, and PGE₂ were evaluated using colorimetric and ELISA methods.

Results Dioscorea alata extract inhibited the expression of NO and TNF-α with an IC₅₀ value of 134.51?±?6.75 and 113.30?±?7.44?μg/mL, respectively. The IC₅₀ values for inhibition of total COX, COX-1, COX-2 activities and PGE₂ level were 41.96?±?3.07, 141.41?±?8.99, 32.50?±?1.69, and 186.34?±?15.36?μg/mL, respectively. Inhibition of PGE₂ level and COX-2 activity was positively correlated (R²?=?0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene.

Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0?μg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract.     

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers

Context: The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system.

Objective: This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats.

Material and methods: Animals were randomized into control, kernel extract (100 and 200?mg/kg/d, orally), dexamethasone (0.03?mg/kg/d, subcutaneously), dexamethasone?+?kernel (100 and 200?mg/kg/d, separately), and dexamethasone?+?captopril (25?mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX).

Results: Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128?±?7 vs. 105?±?3?mmHg, p?p?p?p?Conclusion: Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.     

Changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia

Objective

The present study aimed to examine the changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia.

Methods

Sixty-two drug naïve, first-episode schizophrenia (SZ group) and 60 healthy individuals (control group) were enrolled in the study. Serum interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and body weight were measured at baseline for both groups, and repeated for the SZ group at five different time points during 6-month risperidone treatment.

Results

At baseline, serum IL-1β, IL-6, and TNF-α levels in the SZ group (53.28?±?12.62, 33.98?±?14.13, 50.08?±?12.86 pg/mL, respectively) were significantly higher than those in the control group (23.49?±?15.27, 15.53?±?7.16, 32.12?±?15.23 pg/mL, respectively) (p's?<?0.001). Within the SZ group, serum IL-1β levels decreased significantly at 2 weeks (48.02?±?16.00 pg/mL, p?<?0.01) and 1 month (44.70?±?16.63 pg/mL, p?<?0.001), but then gradually increased at 2 months (48.49?±?18.87 pg/mL), 3 months (50.59?±?18.48 pg/mL) and 6 months (53.64?±?16.22 pg/mL) to the levels comparable to baseline; serum IL-6 levels changed significantly over the course of treatment (p?=?0.001), but reached the levels comparable to baseline at 6 months (37.13?±?13.23 pg/mL); serum levels of TNF-α increased significantly at 3 months (55.02?±?16.69 pg/mL, p?<?0.01) and 6 months (58.69?±?13.57 pg/mL, p?<?0.001); steady and significant weight gain was observed at each follow-up time point (p's?<?0.001), from 56.71?±?9.25 kg at baseline to 62.72?±?9.53 kg at 6 months.

Conclusions

Risperidone treatment is associated with changes in serum pro-inflammatory cytokines levels and weight. There is an initial anti-inflammatory effect that reduces with treatment, potentially due to its weight gain side effect.     

Bioassay guided fractionation and identification of active anti-inflammatory constituent from Delonix elata flowers using RAW 264.7 cells

Abstract

Context: Delonix elata (L.) Gamble (Fabaceae) has been used in the Indian traditional medicine system to treat rheumatism and inflammation.

Aim: To assess the anti-inflammatory effect of Delonix elata flowers and to isolate the active principle.

Materials and methods: The prompt anti-inflammatory constituent was isolated from Delonix elata flower extracts using bioassay guided fractionation in liposaccharide (LPS) stimulated RAW 264.7 macrophage cell line. The anti-inflammatory activity of extracts/fractions/sub-fractions/compounds (10, 25, and 50?µg/ml) was evaluated by estimating the levels of nitric oxide (NO), TNF-α, and IL-1β after 24?h of LPS induction (1?μg/ml). The isolated active compound was subjected to NMR, IR, and UV analyses for structure determination.

Results: In an attempt to search for anti-inflammatory constituents, the active pure principle was isolated and crystallized as a white compound from Delonix elata flowers methanol extract. This active compound (50?µg/ml) decreased the release of inflammatory mediators levels such as NO (0.263?±?0.03?µM), TNFα (160.20?±?17.57?pg/ml), and IL-1β (285.79?±?15.16?pg/ml) significantly (p?<?0.05); when compared to the levels of NO (0.774?±?0.08?µM), TNFα (501.71?±?25.14?pg/ml), and IL-1β (712.68?±?52.25?pg/ml) from LPS-stimulated macrophage cells. The active compound was confirmed as hesperidin with NMR, IR, and UV spectroscopy data. This is the first report of this compound from Delonix elata flowers.

Conclusion: The findings of the study support the traditional use of Delonix elata flowers to treat inflammation.     

Effects of polysaccharide from Physalis alkekengi var. francheti on liver injury and intestinal microflora in type-2 diabetic mice

Context: Diabetic liver injury is a serious diabetic complication. The alterations of intestinal microbiota play an important role in induction and promotion of liver injury progression. Physalis alkekengi L. var. francheti (Mast.) Makino (Solanaceae) has been used as a water decoction for treating diabetes.

Objective: To study the effects of a polysaccharide (PPSB) from Physalis alkekengi var. francheti on liver injury and intestinal microflora in type-2 diabetic mice.

Materials and methods: Streptozotocin (160?mg/kg) was injected i.p. for 3?days to build model. The diabetic mice were randomly divided into four groups together with control group (10 mice in each group). The doses of PPSB were 50 and 100?mg/kg, respectively. After 5 weeks administration, level of blood glucose, ALT and AST were measured. Alterations of intestinal microflora, and protein expression of TGF-β1, TNF-α and DCN were detected.

Results: Level of blood glucose decreased from (25.38?±?2.21) mmol/L to (18.01?±?2.53) mmol/L, ALT and AST decreased to (24.67?±?4.86) U/L and (30.84?±?7.50) U/L in PPSB-H group. Lactobacillus, Clostridium butyricum, and Bacteroides increased remarkably with increasing concentration of PPSB, but Enterobacter was inhibited. The relative expression of TGF-β1 and TNF-α decreased to (0.70?±?0.17) and (0.39?±?0.06), and the expression of DCN increased to (0.65?±?0.13).

Discussion and conclusions: Probiotics have been promoted by PPSB, and protein expressions have been modulated in the progression of liver injury. PPSB could be used as a natural agent for treating diabetic liver injury and intestinal microflora imbalance.