Novel insights into the anti-asthmatic effect of Raphanus sativus L. (Raphani Semen): Targeting immune cells, inflammatory pathways and oxidative stress markers.

ETHNOPHARMACOLOGICAL RELEVANCE: Raphanus sativus L. is a well-known medicinal plant with traditional therapeutic applications in various common ailments including inflammation and asthma. AIMS OF THE STUDY: This study aimed to evaluate the chemical composition and anti-asthmatic potential of the hydro-methanolic extract of the leaves of R. sativus L. (Rs.Cr) using various in vitro and in vivo investigations. MATERIALS AND METHODS: The Rs.Cr was subjected to preliminary phytochemical analysis and HPLC profiling. The safety was assessed through oral acute toxicity tests in mice. The antiasthmatic effect of the extract was studied using milk-induced leukocytosis and ovalbumin (OVA)-induced allergic asthma models established in mice. While mast cell degranulation and passive paw anaphylaxis models were established in rats. Moreover, effect of the extract was studied on various oxidative and inflammatory makers. The antioxidant effect of the extract was also studied by in vitro DPPH method. RESULTS: The HPLC profiling of Rs.Cr showed the presence of important polyphenols in a considerable quantity. In toxicity evaluation, Rs.Cr showed no sign of morbidity or mortality with LD50 < 2000 mg/kg. The extract revealed significant mast cell disruption in a dose-dependent manner compared to the intoxicated group. Similarly, treatment with Rs.Cr and dexamethasone significantly (p < 0.001) reduced paw edema volume. Subcutaneous injection of milk at a dose of 4 mL/kg, after 24 h of its administration, showed an increase in the leukocyte count in the intoxicated group. Similarly, mice treated with dexamethasone and Rs.Cr respectively showed a significant decrease in leukocytes and eosinophils count in the ovalbumin-induced allergic asthma model. The extract presented a significant (p˂0.001) alleviative effect on the levels of SOD and GSH, MDA, IL-4, IL-5, and IL-13 in a dose-dependent manner as compared to the intoxicated group. Furthermore, the histological evaluation also revealed a notable decrease in inflammatory and goblet cell count with reduced mucus production. CONCLUSION: The current study highlights mechanism-based novel insights into the anti-asthmatic potential of R. sativus that also strongly supports its traditional use in asthma.

Anxiolytic and Antidepressant Potential of Methanolic Extract of Neurada procumbens Linn. in Mice.

Neurada procumbens Linn. possesses a wide range of phytochemical and bioactive entities such as flavonoids and polyphenols that decrease the oxidative stress and enhance synaptic plasticity, resulting in accelerated healing processes. Almost all parts of the plant have been used in the traditional system of medicine for various disorders including its use as an anticonvulsant, sexual tonic, and anti-rheumatic agent. This study is designed to evaluate the anxiolytic and antidepressant activities of the methanolic crude extract of N. procumbens (Np.Cr) based on its use in traditional medicine and presence of the phytochemical constituents. Aqueous methanolic extract of Np.Cr was prepared under reduced pressure using rotary evaporator, and different chemical constituents were identified by phytochemical screening. Light/dark exploration, elevated plus maze (EPM), and hole board tests were used to assess the anxiolytic activity, while forced swim and tail suspension tests were used to assess the antidepressant potential of the crude extract. Treatment groups treated individually with 3 different doses; i.e., 50, 100, and 200 mg/kg of Np.Cr, showed a dose-dependent increase in time spent in light compartment and in open arms as well as increased number of head poking by the experimental animals. Np.Cr showed significant antidepressant potential (P < .05) as evident from marked decrease in behavioral despair. Findings of the present study assure that N. procumbens possess significant anxiolytic and antidepressant potential with the demands of further investigations to identify the active compound(s) responsible for these pharmacological effects.

Gisekia pharnaceoides Restores Colonic Mucosal Homeostasis by Regulating Antioxidant Enzyme System and Cytokines Signaling in Ulcerative Colitis Mice Model.

BACKGROUND: Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by the native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. OBJECTIVE: This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. METHODS: The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 µl of 7.5% acetic acid intra- rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score, and hematological parameters. The anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide, and cytokines (IL-1ß, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. RESULTS: Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins, and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores, and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide, and cytokines levels. Histopathological examination showed a significant decline in ulceration and tissue disruption. CONCLUSION: Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.

TGF-ß1 signaling can worsen NAFLD with liver fibrosis backdrop.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of fats in the liver. Relatively benign NAFLD often progresses to fibrosis, cirrhosis, and liver malignancies. Although NAFLD precedes fibrosis, continuous lipid overload keeps fueling fibrosis and the process of disease progression remains unhindered. It is well known that TGF-ß1 plays its part in liver fibrosis, yet its effects on liver lipid overload remain unknown. As TGF-ß1 signaling has been increasingly attempted to manage liver fibrosis, its actions on the primary suspect (NAFLD) are easily ignored. The complex interaction of inflammatory stress and lipid accumulation aided by mediators scuh as pro-inflammatory interleukins and TGF-ß1 forms the basis of NAFLD progression. Anticipatorily, the inhibition of TGF-ß1 signaling during anti-fibrotic treatment should reverse the NAFLD though the data remain scattered on this subject to date. TGF-ß1 signaling pathway is an important drug target in liver fibrosis and abundant literature is available on it, but its direct effects on NAFLD are rarely studied. This review aims to cover the pathogenesis of NAFLD focusing on the role of the TGF-ß1 in the disease progression, especially in the backdrop of liver fibrosis.