Attenuation of CFA-induced arthritis through regulation of inflammatory cytokines and antioxidant mechanisms by Solanum nigrum L. leaves extracts.

Solanum nigrum L. is a popular traditional medicine for various inflammatory conditions including rheumatism and joint pain. The current study aimed to evaluate the anti-arthritic mechanism of Solanum nigrum L. Four extracts were prepared using n-hexane, methanol, chloroform, and water. The anti-nociceptive and anti-inflammatory activity was carried out with 100, 200, and 300 mg/kg body wt. PO of each extract by the hot plate and carrageenan-induced paw oedema methods, respectively. The anti-arthritic study was performed with chloroform and aqueous extracts (300 mg/kg) in complete Freund's adjuvant (CFA)-induced arthritis. Paw size (mm), ankle joint diameter (mm), and latency time (sec) were recorded on day 0 and every 4th day till 28 days. The hematological, inflammatory, and oxidative biomarkers were estimated. Results showed that significant analgesia (p < 0.05) and reduction in paw inflammation were achieved with all extracts. The highest percent inhibition in Carrageenan-induced inflammation was achieved with 300 mg/kg of chloroform (72.19%) and aqueous (71.30%) extracts, respectively. In the CFA model, both extracts showed a significant reduction in paw size and ankle joint diameter (p < 0.05). The RT-qPCR analysis revealed the upregulation of interleukin-4 and interleukin-10, and down-expression of interleukin-1ß, interleukin-6, tumor necrosis factor-α, cycloxygenase-2, nuclear factor-κB, prostaglandin E synthase 2, and interferon-γ. A significant increase in superoxide dismutase, catalase, and glutathione levels was observed. Hence, it is concluded that Solanum nigrum L. leaf extracts regulate the expression of inflammatory markers and improve oxidative stress resulting in the attenuation of CFA-induced arthritis.

Assessment of in vivo antiepileptic potential and phytochemical analysis of Cassia absus seed extracts.

Cassia absus, a member of Fabaceae family, has been a part of traditional medicine for various ailments such as Hypertension, Diabetes, and Cancer. This family of plants has been utilized for Anticonvulsant and Anxiolytic effects. The ongoing investigation is aimed to seek the antiepileptic potential of C. absus seed extracts in pentylenetetrazole-induced kindling mice. The seeds of C. absus were subjected to a sequential extraction process for the preparation of n-hexane, chloroform, methanol, and aqueous extracts. The PTZ-induced kindling model was employed to assess the antiepileptic activity of each extract. Seizure activity and antioxidant biomarkers in the brain tissue such as levels of CAT, SOD, tGSH, and MDA were assessed. Mechanism of action was elucidated by Flumazenil. Through GC-MS analysis, the phytochemical components in the chloroform extract of C. absus were evaluated. The outcomes showed that C. absus extracts markedly reduced the seizure activity in kindling mice. The extracts exhibited significant Antioxidant properties by enhancing the levels of antioxidant biomarkers in the brain tissue such as CAT, SOD, and tGSH, and decreasing the MDA level. The results demonstrated that C. absus extracts showed antiepileptic effects may be via GABA pathway. According to the results of this investigation, C. absus has significant antiepileptic potential in PTZ-induced kindling mice via GABA pathway modulation and combating reactive oxygen species.

Cassia absus-mediated upregulation of IL-4, IL-10 and downregulation of IL-1ß, IL-6, TNF- α, NF-κB, IFN-γ in CFA-induced arthritis model.

Traditional use of Cassia absus as an anti-inflammatory in conjunctivitis and bronchitis is well reported. Owing to its anti-inflammatory potential, the current study appraised in vivo anti-arthritic activity of n-hexane and aqueous extracts of Cassia absus seeds (200 mg/kg) using Complete Freund's Adjuvant (CFA) rat model of arthritis. Changes in paw size (mm), joint diameter (mm), and pain response (sec) were recorded at the baseline and then after CFA induction at the interval of 4 days till the 28th day. Blood samples of anesthetized rats were collected for the estimation of hematological, oxidative, and inflammatory biomarkers. Results showed percent inhibition in paw edema (45.09% and 60.79%) with both n-hexane and aqueous extracts, respectively. Significant reduction in paw size and ankle joint diameter (P < 0.01) was seen in extracts treated rats. Erythrocyte Sedimentation rate, C-Reactive Protein, White Blood Cell levels significantly lowered, and Hemoglobin, Platelets and Red Blood Cell count significantly increased post-treatments. Superoxide Dismutase, Catalase, and Glutathione were significantly improved (P < 0.0001) in treated groups as compared to CFA induced arthritic control. Real-time polymerase chain reaction investigation showed significant downregulation (P < 0.05) of Interleukin-1ß, Tumor Necrosis Factor-α, Interleukin-6, Cycloxygenase-2, Nuclear Factor-κB, Prostaglandin E Synthase 2, Interferon Gamma and upregulation of Interleukin-4, Interleukin-10 in both n-hexane and aqueous extract-treated groups. It is thereby concluded that Cassia absus can significantly attenuate CFA-induced arthritis by modulation of oxidative and inflammatory biomarkers.

Metabolic Profiling and Investigation of the Modulatory Effect of Fagonia cretica L. Aerial Parts on Hepatic CYP3A4 and UGT2B7 Enzymes in Streptozotocin-Induced Diabetic Model.

Drug-metabolizing enzymes are either boosted or suppressed by diabetes mellitus. This research was designed to explore Fagonia cretica L. aerial parts' impact on CYP3A4 and UGT2B7 activity and their mRNA expression in diabetic rats. Fagonia cretica (F. cretica) dried powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, methanol, and water. The methanol extract and aqueous fraction presented the most significant potential to decrease the concentration of alpha-hydroxyl midazolam, with 176.0 ± 0.85 mg/Kg and 182.9 ± 0.99 mg/Kg, respectively, compared to the streptozotocin (STZ)-induced diabetic group, reflecting the inhibition in CYP3A4 activity. The fold change in mRNA expression of CYP3A4 was decreased significantly by the methanol extract, and the aqueous fraction of F. cretica estimated by 0.15 ± 0.002 and 0.16 ± 0.001, respectively, compared with the diabetic group. Morphine metabolism was significantly increased in rats treated with F. cretica methanol extract and its aqueous fraction, displaying 93.4 ± 0.96 mg/Kg and 96.4 ± 1.27 mg/Kg, respectively, compared with the metabolism of morphine in the diabetic group, which highlights the induction of UGT2B7 activity. The fold change in mRNA expression of UGT2B7 was significantly increased by the methanol extract and the aqueous fraction, estimated at 8.14 ± 0.26 and 7.17 ± 0.23 respectively, compared to the diabetic group. Phytochemical analysis was performed using high-performance liquid chromatography (HPLC), where the methanol extract showed more flavonoids and phenolic compounds compared to the aqueous fraction of F. cretica. The obtained results were further consolidated by molecular docking studies, where quercetin showed the best fitting within the active pocket of CYP3A4, followed by gallic acid, displaying free binding energies (∆G) of -30.83 and -23.12 kcal/mol, respectively. Thus, F. cretica could serve as a complementary medicine with standard anti-diabetic therapy that can modulate the activity of the drug-metabolizing enzymes.

Evaluation of the Anxiolytic and Anti-Epileptogenic Potential of Lactuca Serriola Seed Using Pentylenetetrazol-Induced Kindling in Mice and Metabolic Profiling of Its Bioactive Extract.

This study aimed to assess the potential of Lactuca serriola (Asteraceae) seed n-hexane, chloroform, methanol, and aqueous extracts as anticonvulsant, sedative, anticonvulsant and antiepileptic agents in Swiss albino mice. Different doses of each extract were evaluated for the anxiolytic potential using the hole-board, the elevated plus maze and the light/dark test. A phenobarbitone-induced sleep test was employed for the evaluation of sedative potential. Acute anticonvulsant activity was evaluated by picrotoxin and strychnine-induced convulsion models. All extracts significantly reduced the number of head dips where n-hexane extract (400 mg/kg) showed 96.34% reduction in the tendency of head dipping when compared with the control. Mice treated with extracts preferred elevated plus maze open arms and were shown to lack open arms evasion, especially n-hexane extract (400 mg/kg)-which showed 456.14%-increased the duration of open arm stay with the respective control group. By reducing sleep latency and greatly lengthening sleep duration, L. serriola enhanced the effects of barbiturate-induced sleep. A significant increase in convulsion latency and decrease in convulsions induced by picrotoxin and strychnine duration was observed in all extract-treated groups. All the extracts exhibited anti-epileptogenic potential as the seizure score in pentylenetetrazol (PTZ)-induced kindling in mice was reduced significantly. Maximum protection was afforded by chloroform extract that reduced the seizure score by 79.93% compared with the PTZ group. Chloroform executed antioxidant effect by elevating super oxide dismutase (SOD) by 126%, catalase (CAT) by 83.53%, total glutathione (tGSH) by 149%, and reducing malondialdhyde (MDA) levels by 36.49% in the brain tissues that is further consolidated by histopathological examination. Metabolic profiling of the most active chloroform extract using Gas chromatography coupled with mass showed the presence of 16 compounds. This anti-epileptic activity was further confirmed via in silico molecular modelling studies in the active site Gamma-aminobutyric acid aminotransferase (GABA-AT) where all of the tested metabolites illustrated a potent inhibitory potential towards GABA-AT with hexadecanoic acid, 15-methyl-, methyl ester followed by octadecanoic acid, methyl ester showed the best fitting. The results indicated the possible anxiolytic and anti-epileptogenic potential of the plant and further consolidated the ethnopharmacological use of L. serriola seeds.