Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention.

Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00370-1.

Molecular and pharmacological aspects of piperine as a potential molecule for disease prevention and management: evidence from clinical trials.

BACKGROUND: Piperine is a type of amide alkaloid that exhibits pleiotropic properties like antioxidant, anticancer, anti-inflammatory, antihypertensive, hepatoprotective, neuroprotective and enhancing bioavailability and fertility-related activities. Piperine has the ability to alter gastrointestinal disorders, drug-metabolizing enzymes, and bioavailability of several drugs. The present review explores the available clinical and preclinical data, nanoformulations, extraction process, structure-activity relationships, molecular docking, bioavailability enhancement of phytochemicals and drugs, and brain penetration properties of piperine in the prevention, management, and treatment of various diseases and disorders. MAIN BODY: Piperine provides therapeutic benefits in patients suffering from diabetes, obesity, arthritis, oral cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Parkinson's disease, Alzheimer's disease, cerebral stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The molecular basis for the pleiotropic activities of piperine is based on its ability to regulate multiple signaling molecules such as cell cycle proteins, anti-apoptotic proteins, P-glycoprotein, cytochrome P450 3A4, multidrug resistance protein 1, breast cancer resistance protein, transient receptor potential vanilloid 1 proinflammatory cytokine, nuclear factor-κB, c-Fos, cAMP response element-binding protein, activation transcription factor-2, peroxisome proliferator-activated receptor-gamma, Human G-quadruplex DNA, Cyclooxygenase-2, Nitric oxide synthases-2, MicroRNA, and coronaviruses. Piperine also regulates multiple signaling pathways such as Akt/mTOR/MMP-9, 5'-AMP-activated protein kinase-activated NLR family pyrin domain containing-3 inflammasome, voltage-gated K+ current, PKCα/ERK1/2, NF-κB/AP-1/MMP-9, Wnt/ß-catenin, JNK/P38 MAPK, and gut microbiota. SHORT CONCLUSION: Based on the current evidence, piperine can be the potential molecule for treatment of disease, and its significance of this molecule in the clinic is discussed.