Natural products derived steroids as potential anti-leishmanial agents; disease prevalence, underlying mechanisms and future perspectives.

Leishmaniasis is a vector-borne infection caused by protozoan parasites from the genus leishmania and is among the most neglected tropical diseases. It is highly prevalent disease, affecting about 350 million population worldwide. Only limited number of anti-leishmanial agents are approved for clinical use till now and they are associated with side effects and have limited efficacy. Subsequently, natural products based discovery of more safe and effective drugs against leishmania is under scientific consideration. Various studies reported the efficacy of natural products against intracellular and extracellular forms of leishmania species. This work is aimed to evaluate current literature focused on the anti-leihmanial efficacy of steroidal moieties from natural products and their mechanism of action. Compounds including steroidal saponins, steroidal alkaloids and phytosterols were found to exhibit considerable anti-leishmanial efficacy. For instance, steroidal saponin, (25R)-spirost-5-en-3b-ol,3-O-α-rhamnopyranosyl-(1 â†’ 4)-α-rhamnopyranosyl-(1 â†’ 4)-[a-rhamnopyranosyl-(1 â†’ 2)]-glucopyranoside isolated from A. paradoxum has completely eradicated Leishmania major promastigotes at 50 µg mL-1 dose. Spirostanic saponins isolated from Solanum paniculatum L. were effective against Leishmania amazonensis promastigotes. Turgidosterones isolated from Panicum turgidum exhibited high leishmanicidal potentials against Leishmania donovani promastigotes with IC50 of 4.95-8.03 µg mL-1 and even better activity against amastigotes exhibiting an IC50 of 4.50-9.29 µg mL-1. Likewise, racemoside-A from Asparagus racemosus was found effective against an antimonial sensitive (AG83) and antimonial resistant (GE1F8R) strains of the L. donovani. Moreover, steroidal alkaloids including hookerianamide-1, hookerianamide-H, hookerianamide-J, hookerianamide-K, dehydrosarsalignone, vagenine-A, sarcovagine-C, holaphylline, saracodine, holamine, 15-α hydroxyholamine, holacurtin, N-desmethyl holacurtine and elasticine has exhibited time and dose-dependent efficacy against various strains of leishmania. ß-sitosterol was found active against multiple strains of leishmania. These compounds mainly exhibit their therapeutic efficacy via liberation of ROS, mitochondrial depolarization, morphological and ultra-structural changes, accumulation of lipid droplets, depletion of non-protein thiols and triggering apoptotic pathways. In conclusion, leishmaniasis is a major health problem in many countries. Plants-derived steroids moieties have reveled efficacy against leishmaniasis and is a source of lead compounds. Further detailed molecular studies are warranted for the discovery of more effective and safe anti-leishmanial drugs.

Alzheimer's Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms.

Saponins are triterpenoid or steroidal glycosides and are an important group of naturally occurring compounds of plant origin. They exhibit diverse pharmacological potentials including radical scavenging, as well as neuroprotective, anti-diabetic and anti-inflammatory activities, owing to their diverse chemical scaffolds. Saponins consist of an aglycone part (non-sugar) and a glycone part (sugar) and have at least one glycosidic (C-O sugar bond) linkage present between the glycone and aglycone mostly at C-3. On the basis of the aglycone part, saponins are classified into triterpenoid glycosides, steroid glycosides and alkaloid glycosides. Saponins exhibit neuroprotective activities against various disorders of the central nervous system (CNS) including stroke, Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). They mediate their therapeutic effects by modulation of various pathological targets. This study highlights various neuroprotective mechanisms of saponins including free radical scavenging, modulation of neuroprotective signaling pathways, activation of neurotrophic factors, modulation of neurotransmitters, inhibition of BACE1 enzyme and tau hyper-phosphorylation. The study concludes that saponins have considerable efficacy against various pathological targets of neurological disorders, especially AD, and might be an important source of leads against neurodegenerative disorders.