AimTo compare stress resistance increasing and analgesic activities of piperlongumine and a methanolic Piper longum fruit extract (PLE).MethodsEfficacies of a single and repeated daily oral doses (1–256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline against foot shock stress triggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activity in tail suspension test and on pentobarbital induced sedation in male mice were compared. In another experiment, analgesic activities of single and repeated daily 5 mg/kg oral doses of piperlongumine and PLE in mice hot plate test and in acetic acid induced writing tests were compared with those of aspirin and doxycycline.ResultsAfter their single oral doses no effects of piperlongumine or PLE or doxycycline were observed in the footshock stress induced hyperthermia test or in hot plate test. However, significant effects of piperlongumine and PLE in both the tests were observed after their 5 or more daily doses. Both of them also dose dependently suppressed daily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activity in tail suspension test and aspirin like analgesic effects in acetic acid writhing test were observed after their 11 daily 5 mg/kg oral dose.ConclusionPiperlongumine is another bioactive secondary metabolite of P. longum and other plants of piper species with stress response suppressing, analgesic, and anti-inflammatory activities. Its bactericidal activities can also contribute to its therapeutically interesting bio-activity profile.
Alzheimer's disease is identified by pathological hallmarks such as intracellular neurofibrillary tangles (NFTs) and extracellular amyloid β plaques. Several hypotheses exist to define the neurodegeneration including microglial activation associated with neuroinflammatory processes. Recently, pharmacological inhibition of endocannabinoid (eCB)-degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), is being investigated to modulate the pathology of Alzheimer's disease. While MAGL inhibitors upregulate 2-acyl glycerol (2-AG) levels and reduce neuroinflammation, FAAH inhibitors elevate anandamide (AEA) levels and prevent the degradation of HSP-70, thereby preventing the phosphorylation of tau protein and formation of NFTs in neural cells. We investigated the possible neuroprotective potential of the dual MAGL/FAAH inhibitor JZL-195 (20 mg/kg) against ICV-STZ-induced sporadic Alzheimer's disease (SAD) in Swiss albino mice using donepezil (5 mg/kg) as the standard. The protective effects of JZL-195 were observed by the reversal of altered levels of Aβ 1−42 , HSP-70, neuroinflammatory cytokines, and oxidative stress markers. However, JZL-195 expressed no cognitive improvement when assessed by spontaneous alternation behavior and Morris water maze tests and no effects on the AChE enzyme level in the hippocampal tissues of mice. Therefore, the findings of the present study indicate that although JZL-195 exhibited no improvement in cognitive deficits associated with sporadic Alzheimer's disease, it displayed significant reversal of the biochemical anomalies, thereby suggesting its therapeutic potential against the sporadic Alzheimer's disease model.
Aim:To compare doxycycline (DOX) such as oral efficacies of piperlongumine (PL) and a Piper longum fruits extract (PLE) as stress resistance inducers.Materials and Methods:Efficacies of oral pretreatments with 5 mg/kg PL or PLE or of 50 mg/kg DOX for 10 consecutive days against stress resistance were compared. Mice in treated groups were subjected to a stress induced hyperthermia on the 1st, 5th, 7th, and 10thday. Treated mice were then subjected to tail suspension test on the 11thday. Alteration in body weights, core temperatures, and gastric ulcers triggered by occasional exposures to foot shocks were determined.Results:DOX like long-lasting protective effects of PL and PLE against gradual alterations in body weights, basal temperatures and transient hyperthermic responses triggered by foot shocks during the post-treatment days were observed. Altered responses of stressed mice in tail suspension test observed 1 day after the last foot-shock exposures and gastric ulcers and other pathologies quantified 1 day after the test were also suppressed in PL or PLE or DOX pretreated groups.Conclusion:PL and crude PLE are DOX like long-acting desensitizers of stress triggered co-morbidities. Reported observations add further experimental evidences justifying traditionally known medicinal uses of P. longum and other plants of the Piperaceae family, and reveal that PL is also another very long acting and orally active inducer of stress resistance. Efforts to confirm stress preventive potentials of low dose plant-derived products enriched in PL or piperine like amide alkaloids in volunteers and patients can be warranted.
Medicinal uses of edible and other plants for prevention and cure of obesity and overweight associated metabolic and mental health problems have since long been known to scholars and practitioners of Ayurvedic and other traditionally known system of medicine. Modernized versions of numerous edible plant derived formulations mentioned in ancient Ayurvedic texts are at present some of the most popular, or best selling, herbal remedies in India and numerous other countries suffering from double burden of diseases caused by malnutrition and obesity. Preclinical and clinical information now available on edible plants and their bioactive constituents justify traditionally known medicinal uses of products derived from them for prevention and cure of obesity associated type-2 diabetes, psychopathologies and other health problems. Such information now available on a few edible Ayurvedic plants and their formulations and suggesting that their stress response regulating effects are involved in their broad spectrums of bioactivity profiles are summarized in this communication. Implications of recent physiological and pharmacological observations made with numerous phytochemicals isolated from edible plants for better understanding of traditionally known medicinal uses of herbal remedies are also pointed out.
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