Recent advances in the biosynthesis, bioavailability, toxicology, pharmacology, and controlled release of citrus neohesperidin.

Neohesperidin (hesperetin 7-O-neohesperidoside), a well-known flavanone glycoside widely found in citrus fruits, exhibits a variety of biological activities, with potential applications ranging from food ingredients to therapeutics. The purpose of this manuscript is to provide a comprehensive overview of the chemical, biosynthesis, and pharmacokinetics profiles of neohesperidin, as well as the therapeutic effects and mechanisms of neohesperidin against potential diseases. This literature review covers a wide range of pharmacological responses elicited by Neohesperidin, including neuroprotective, anti-inflammatory, antidiabetic, antimicrobial, and anticancer activities, with a focus on the mechanisms of those pharmacological responses. Additionally, the mechanistic pathways underlying the compound's osteoporosis, antiulcer, cardioprotective, and hepatoprotective effects have been outlined. This review includes detailed illustrations of the biosynthesis, biopharmacokinetics, toxicology, and controlled release of neohesperidine. Neohesperidin demonstrated a broad range of therapeutic and biological activities in the treatment of a variety of complex disorders, including neurodegenerative, hepato-cardiac, cancer, diabetes, obesity, infectious, allergic, and inflammatory diseases. Neohesperidin is a promising therapeutic candidate for the management of various etiologically complex diseases. However, further in vivo and in vitro studies on mechanistic potential are required before clinical trials to confirm the safety, bioavailability, and toxicity profiles of neohesperidin.

Subacute oral toxicity of ayurvedic anti-diabetic preparation Jambadyarista in Sprague-Dawley rats.

BACKGROUND: Jambadyarista is an Ayurvedic polyherbal formulation widely prescribed by Ayurvedic practitioners for the management of diabetes and its associated complications. About 39 companies have marketed this formulation in Bangladesh with consent from the Directorate General of Drug Administration (DGDA). AIM: This study investigated the sub-acute oral toxicity of Jambadyarista in the Sprague-Dawley rat model. METHODS: The sub-acute toxicity studies were executed in Sprague-Dawley rats. Jambadyarista formulation was given for 28-days through oral gavage at 10 mL/kg and 20 mL/kg dose to two different groups comprising 6 rats of both sex/groups. Across the experimental period mortality, adverse reactions were closely monitored. After 28-day feeding hematological, biochemical, and relative organ weights were quantified. RESULTS: No mortality and/or signs of morbidity were observed for 28-day of repeated-dose sub-acute toxicity. Any pernicious change in body weight, biochemical, and hematological parameters along with relative organ weight were not observed for Jambadyarista. Correlation study among parameters of the renal profile, liver profile, lipid profile also metabolic hormones (T3 and TSH), and enzymes showed the non-toxic rather beneficial role (hypolipidemic) of Jambadyarista in Sprague-Dawley rats. CONCLUSION: Jambadyarista preparation did not cause any potential toxic effect in repeated dose subacute toxicity study over Sprague-Dawley rats orally. Therefore, low dose administration of Jambadyarista could have a beneficial effect on diabetes and can be considered safe before the chronic study.

Curculigo recurvata W.T.Aiton exhibits anti-nociceptive and anti-diarrheal effects in Albino mice and an in silico model.

BACKGROUND: Curculigo recurvata (C. recurvata) is an enthnomedicinally important herb reported to have significant medicinal values. The present study aimed to explore the in vivo and in silico anti-nociceptive and anti-diarrheal effects of a C. recurvate rhizome methanol extract (Me-RCR). METHODS: The analgesic effects of Me-RCR were assessed using acetic acid-induced writhing and the formalin-induced flicking test. The drugs were administered intraperitoneally (IP) at doses of 200 and 400 mg/kg body weight (bw). Anti-diarrheal activity was evaluated by assessing intestinal motility, hypersecretion, and fecal score in mice at oral doses of 200 and 400 mg/kg·bw. Computer facilitated analyses for anti-nociceptive and anti-diarrheal activities of three isolated compounds from C. recurvata were undertaken to identify the best-fit phytoconstituents. RESULTS: The Me-RCR showed significant (P < .05) peripheral anti-nociception at the highest dose. The extract inhibited both early and late phases of nociception in the formalin-induced writhing test. In the castor oil-induced diarrhoea model, the extract significantly (P < .05) prolonged the onset time of diarrhoea, inhibited percentage of diarrhoea, and decreased both the volume and weight of intestinal contents. Rates of intestinal fluid accumulation inhibition were (33.61 ± 1.00)% and (46.44 ± 0.89)% at Me-RCR doses of 200 and 400 mg/kg·bw, respectively. Moreover, a significant (P < .05) reduction in gastrointestinal motility was observed. An absorption, distribution, metabolism, excretion and/or toxicity (ADME/T) test showed that the selected compounds yielded promising results, satisfying Lipinski's rule of five for predicting drug-like potential. Notably, of the three phytoconstituents curculigine and isocurculigine possessed the highest affinity for the COX-1 and COX-2. Isocurculigine was also identified as the most effective anti-diarrheal compound in the computer-facilitated model. CONCLUSION: An extract of the plant C. recurvata showed potential analgesic and anti-diarrheal activity due to the presence of one or more active secondary metabolite(s).

Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models.

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking) analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal) displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models.

Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice.

BACKGROUND: The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. METHODS: In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. RESULTS: The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. CONCLUSIONS: These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.