Investigating the Potential Therapeutic Mechanisms of Puerarin in Neurological Diseases.

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, ß-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.

Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.

Computational exploration of Zika virus RNA-dependent RNA polymerase inhibitors: a promising antiviral drug discovery approach.

The emergence of the Zika virus, which belongs to the Flaviviridae family, became a significant worldwide health issue due to its link with severe neurological complications. The RNA-dependent RNA polymerase (RdRp) of the Zika virus plays a significant part in the replication of the virus and is considered a promising candidate for antiviral drug identification. In this study, we employed computer-based drug discovery approaches to identify potential natural compounds that could act as inhibitors against the RdRp protein of the Zika virus. A comprehensive virtual screening strategy was implemented using the MTiOpenScreen webserver to identify natural compounds from the NP-Lib database. Four natural compounds having the ZINC ID - ZINC000253499147, ZINC000299817665, ZINC000044404209, and ZINC000253388535 were selected based on the binding score revealed during virtual screening. Molecular docking simulations of these selected compounds and reference compounds were performed to assess the binding affinities and the molecular bonds formed during the docking. Additionally, molecular dynamics (MD) simulations, endpoint free binding energy calculation and principal component analysis (PCA) were performed to evaluate the stability and dynamics of the protein-ligand complexes. These compounds exhibited favourable binding energies and formed stable interactions within the active site of the RdRp protein. Moreover, the molecular dynamics simulations revealed the robustness of the protein-ligand complexes, suggesting the potential for sustained inhibition. These findings provide valuable insights for the design and development of novel therapeutic interventions against Zika virus infection. Further experimental validation and optimization of the identified compounds are warranted to advance their potential translation into effective antiviral drugs.Communicated by Ramaswamy H. Sarma.

Evaluation of Antidiabetic, Antioxidant and Anti-Hyperlipidemic Effects of Solanum indicum Fruit Extract in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: Globally, diabetes mellitus is the most common cause of premature mortality after cardiovascular diseases and tobacco chewing. It is a heterogeneous metabolic disorder characterised by the faulty metabolism of carbohydrates, fats and proteins as a result of defects in insulin secretion or resistance. It was estimated that approximately 463 million of the adult population are suffering from diabetes mellitus, which may grow up to 700 million by 2045. Solanum indicum is distributed all over India and all of the tropical and subtropical regions of the world. The different parts of the plant such as the roots, leaves and fruits were used traditionally in the treatment of cough, asthma and rhinitis. However, the hypoglycaemic activity of the plant is not scientifically validated. PURPOSE: The present study aimed to evaluate the antioxidant, antidiabetic and anti-hyperlipidaemic activity of methanolic fruit extract of Solanum indicum (SIE) in streptozotocin (STZ) induced diabetic rats. METHOD: Experimentally, type II diabetes was induced in rats by an i.p. injection of STZ at a dose of 60 mg/kg. The effect of the fruit extract was evaluated at doses of 100 and 200 mg/kg body weight in STZ-induced diabetic rats for 30 days. RESULT: The oral administration of fruit extract caused a significant (p < 0.05) reduction in the blood glucose level with a more prominent effect at 200 mg/kg. The fruit extract showed dose-dependent α-amylase and α-glycosidase inhibitory activity. It reduced the serum cholesterol and triglyceride levels remarkably in diabetic rats compared to normal. The extract showed the reduced activity of endogenous antioxidants, superoxide dismutase, glutathione peroxidase and catalase in the liver of STZ diabetic rats. CONCLUSION: The result confirmed that the fruit extract of Solanum indicum showed a dose-dependent blood glucose lowering effect and significantly reduced elevated blood cholesterol and triglycerides. It prevented oxidative stress associated with type II diabetes in STZ rats.

Neuropharmacological interventions of quercetin and its derivatives in neurological and psychological disorders.

Quercetin is a naturally occurring bioactive flavonoid abundant in many plants and fruits. Quercetin and its derivatives have shown an array of pharmacological activities in preclinical tests against various illnesses and ailments. Owing to its protective role against oxidative stress and neuroinflammation, quercetin is a possible therapeutic choice for the treatment of neurological disorders. Quercetin and its derivatives can modulate a variety of signal transductions, including neuroreceptor, neuroinflammatory receptor, and redox signaling events. The research on quercetin and its derivatives in neurology-related illnesses mainly focused on the targets, such as redox stress, neuroinflammation, and signaling pathways; however, the function of quercetin and its derivatives on specific molecular targets, such as nuclear receptors and proinflammatory mediators are yet to be explored. Findings showed that various molecular targets of quercetin and its derivatives have therapeutic potential against psychological and neurodegenerative disorders.

Molecular Mechanism and Role of Japanese Encephalitis Virus Infection in Central Nervous System-Mediated Diseases.

The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion people are at risk, and thousands suffer from permanent neurological disorders across Asian countries, with 10-15 thousand people dying each year. JEV crosses the blood-brain barrier (BBB) and forms a complex with receptors on the surface of neurons. GRP78, Src, TLR7, caveolin-1, and dopamine receptor D2 are involved in JEV binding and entry into the neurons, and these receptors also play a role in carcinogenic activity in cells. JEV binds to GRP78, a member of the HSP70 overexpressed on malignant cells to enter neurons, indicating a higher chance of JEV infection in cancer patients. However, JEV enters human brain microvascular endothelial cells via an endocytic pathway mediated by caveolae and the ezrin protein and also targets dopamine-rich areas for infection of the midbrain via altering dopamine levels. In addition, JEV complexed with CLEC5A receptor of macrophage cells is involved in the breakdown of the BBB and central nervous system (CNS) inflammation. CLEC5A-mediated infection is also responsible for the influx of cytokines into the CNS. In this review, we discuss the neuronal and macrophage surface receptors involved in neuronal death.

Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia.

Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the "À La Mode Classification". In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described.

Osteogenic and Chondrogenic Potential of Periosteum-Derived Mesenchymal Stromal Cells: Do They Hold the Key to the Future?

The periosteum, with its outer fibrous and inner cambium layer, lies in a dynamic environment with a niche of pluripotent stem cells for their reparative needs. The inner cambium layer is rich in mesenchymal progenitors, osteogenic progenitors, osteoblasts, and fibroblasts in a scant collagen matrix environment. Their role in union and remodeling of fracture is well known. However, the periosteum as a source of mesenchymal stem cells has not been explored in detail. Moreover, with the continuous expansion of techniques, newer insights have been acquired into the roles and regulation of these periosteal cells. From a therapeutic standpoint, the periosteum as a source of tissue engineering has gained much attraction. Apart from its role in bone repair, analysis of the bone-forming potential of periosteum-derived stem cells is lacking. Hence, this article elucidates the role of the periosteum as a potential source of mesenchymal stem cells along with their capacity for osteogenic and chondrogenic differentiation for therapeutic application in the future.

Accentuating the sources of mesenchymal stem cells as cellular therapy for osteoarthritis knees-a panoramic review.

The large economic burden on the global health care systems is due to the increasing number of symptomatic osteoarthritis (OA) knee patients whereby accounting for greater morbidity and impaired functional quality of life. The recent developments and impulses in molecular and regenerative medicine have paved the way for inducing the biological active cells such as stem cells, bioactive materials, and growth factors towards the healing and tissue regenerative process. Mesenchymal stem cells (MSCs) act as a minimally invasive procedure that bridges the gap between pharmacological treatment and surgical treatment for OA. MSCs are the ideal cell-based therapy for treating disorders under a minimally invasive environment in conjunction with cartilage regeneration. Due to the worldwide recognized animal model for such cell-based therapies, global researchers have started using the various sources of MSCs towards cartilage regeneration. However, there is a lacuna in literature on the comparative efficacy and safety of various sources of MSCs in OA of the knee. Hence, the identification of a potential source for therapeutic use in this clinical scenario remains unclear. In this article, we compared the therapeutic effects of various sources of MSCs in terms of efficacy, safety, differentiation potential, durability, accessibility, allogenic preparation and culture expandability to decide the optimal source of MSCs for OA knee.

Insights Into the Vaginismus Treatment by Cognitive Behavioral Therapies: Correlation With Sexual Dysfunction Identified in Male Spouses of the Patients.

Objective: To examine retrospectively sexual dysfunction in the male spouses of 425 female patients who had presented to our clinic and were diagnosed with primary vaginismus. Materials and methods: Seven questions related to age, profession, educational status, number of marriages, personality structure, sexual experience, and sexual dysfunction history were directed to the spouses of the 425 female patients presenting to our clinic for vaginismus treatment between 2015 and 2018. Men reporting sexual dysfunction were evaluated by a urologist, and the necessary treatment was initiated. Cognitive-behavioral couple therapy was started for all patients. Results: Of the 425 men, 73.9% stated that they did not have any sexual problems. Of the 111 men (26.1%) stated that they had one or more sexual problems, 77 (18.1%) were diagnosed with premature ejaculation, 25 (5.8%) erectile dysfunction, 36 (8.4%) hypoactive sexual desire, and one (0.2%) had delayed ejaculation. Premature ejaculation and erectile dysfunction were identified in nine patients, premature ejaculation and hypoactive sexual desire in seven, and erectile dysfunction and hypoactive sexual desire in four patients. There was an increased rate of sexual dysfunction in men in cases where the duration of marriage without coitus was longer than three years. Conclusion: In the treatment of vaginismus, male sexual dysfunction should not be ignored. Spouses should be questioned for sexual dysfunction and included in the treatment process.

Nanoparticulate RNA delivery systems in cancer.

BACKGROUND: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). RECENT FINDINGS: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. CONCLUSION: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.