Future aspects of plant derived bioactive metabolites as therapeutics to combat benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower urinary tract symptoms (LUTS). Currently, several therapeutic options are accessible for treating BPH, including medication therapy, surgery and watchful waiting. Conventional drugs such as finasteride and dutasteride are used as 5α-reductase inhibitors for the treatment of BPH. However long-term use of these drugs is restricted due to their unpleasant side effects. Despite the range of available medical therapies, the effective treatment against BPH is still inadequate. Certain therapeutic plants and their phytochemicals have the aforementioned goals and work by regulating this enzyme. AIM OF THE STUDY: This review aims to provide a comprehensive insight to advancements in diagnosis of BPH, modern treatment methods and the significance of ethnobotanically relevant medicinal plants as alternative therapeutics for managing BPH. MATERIAL AND METHODS: A thorough and systematic literature search was performed using electronic databases and search engines such as PubMed, Web of Science, NCBI and SciFinder till October 2023. Specific keywords such as "benign prostatic hyperplasia", "medicinal plants", "phytochemicals", "pharmacology", "synergy", "ethnobotany", "5-alpha reductase", "alpha blocker" and "toxicology". By include these keywords, a thorough investigation of pertinent papers was assured, and important data about the many facets of BPH could be retrieved. RESULTS: After conducting the above investigation, 104 herbal remedies were found to inhibit Phosphodiesterase-5 (PDE-5) inhibition, alpha-blockers, or 5α -reductase inhibition effects which are supported by in vitro, in vivo and clinical trial studies evidence. Of these, 89 plants have ethnobotanical significance as alpha-blockers, alpha-reductase inhibition, or PDE-5 inhibition, and the other fifteen plants were chosen based on their ability to reduce BPH risk factors. Several phytocompounds, including, rutaecarpine, vaccarin, rutin, kaempferol, ß-sitosterol, quercetin, dicaffeoylquinic acid, rutaevin, and phytosterol-F have been reported to be useful for the management of BPH. The use of combination therapy offers a strong approach to treating long-term conditions compare to single plant extract drugs. Furthermore, several botanical combinations such as lycopene and curcumin, pumpkin seed oil and saw palmetto oil, combinations of extracts from Funtumia africana (Benth.) Stapf and Abutilon mauritianum (Jacq.) Medik., and Hypselodelphys poggeana (K.Schum.) Milne-Redh. and Spermacoce radiata (DC.) Sieber ex Hiern are also supported through in vitro and in vivo studies for managing BPH through recuperation in patients with chronic long-term illnesses, as measured by the International Prostate Symptom Score. CONCLUSION: The review proposes and endorses careful utilization of conventional medications that may be investigated further to discover possible PDE-5, 5 alpha-reductase, an alpha-blocker inhibitor for managing BPH. Even though most conventional formulations, such as 5 alpha-reductase, are readily available, systemic assessment of the effectiveness and mechanism of action of the herbal constituents is still necessary to identify novel chemical moieties that can be further developed for maximum efficacy. However, there exist abundant botanicals and medicinal plants across several regions of Africa, Asia, and the Americas, which can be further studied and developed for utilization as a potential phytotherapeutic for the management of BPH.

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets.

Prolonged inflammation leads to the genesis of various inflammatory diseases such as atherosclerosis, cancer, inflammatory bowel disease, Alzheimer's, etc. The uncontrolled inflammatory response is characterized by the excessive release of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1alpha (IL-1α), and inflammatory enzymes such as cyclooxygenase-2 (COX-2). Hence, the downregulation of these inflammatory mediators is an active therapy to control aberrant inflammation and tissue damage. To address this, herein, we present the rational design and synthesis of novel phytochemical entities (NPCEs) through strategic linker-based molecular hybridization of aromatic/heteroaromatic fragments with the labdane dialdehyde, isolated from the medicinally and nutritionally significant rhizomes of the plant Curcuma amada. To validate the anti-inflammatory potential, we employed a comprehensive in vitro study assessing its inhibitory effect on the COX-2 enzyme and other inflammatory mediators, viz., NO, TNF-α, IL-6, and IL-1α, in bacterial lipopolysaccharide-stimulated macrophages, as well as in-silico molecular modeling studies targeting the inflammation regulator COX-2 enzyme. Among the synthesized novel compounds, 5f exhibited the highest anti-inflammatory potential by inhibiting the COX-2 enzyme (IC50 = 17.67 ± 0.89 µM), with a 4-fold increased activity relative to the standard drug indomethacin (IC50 = 67.16 ± 0.17 µM). 5f also significantly reduced the levels of LPS-induced NO, TNF-α, IL-6, and IL-1α, much better than the positive control. Molecular mechanistic studies revealed that 5f suppressed the expression of COX-2 and pro-inflammatory cytokine release dose-dependently, which was associated with the inhibition of the NF-κB signaling pathway. This infers that the labdane derivative 5f is a promising lead candidate as an anti-inflammatory agent to further explore its therapeutic landscape.

Ethnobotanical significance of medicinal plants: Beta-amyloid and tau aggregation inhibitors against Alzheimer's disease.

Among the various neurodegenerative disorders, Alzheimer's disease (AD) is identified as one of primary causes of dementia in the elderly, which progresses slowly leading to cognitive decline and ability to function independently. Although various pathological mechanisms have been proposed, the exact mechanism is not yet elucidated. Numerous processes such as old age, mitochondrial dysfunction, and genetics lead to the aggregation of beta-amyloid (Aß) as amyloid plaques and tau proteins as neurofibrillary tangles in the neurons leading to their death and destruction, finally leading to AD. The current treatment measures can only temporarily improve the symptoms, slowing cognitive decline without any effect on AD pathology for better therapeutic effect. Furthermore, the high failure rates of a number of drugs during clinical trials due to their side effects has led the researchers to focus on alternative sources for drug development. As natural ingredients were considered the primary line of treatment in the olden days, and as several medicinal plant products are also proven as effective AD targets, it will be wise to investigate those with significant ethnobotanical value as potential neuroprotectives, nootropics or memory boosters. Throughout the study, propanoids, glycosides, iridoids, carotenoids and flavonoids that show potential anti-inflammatory, antioxidant, and anti-cholinesterase were also found to be inhibitors of Aß and tau aggregation, where Saikosaponin C, Fisetin, and Morin can act as dual inhibitors. The review provides an insight in the need for proper and complete scientific evaluation of these ethnobotanically useful medicinal plants to be identified as potential leads in AD therapy.

Marine Based Natural Products: Exploring the Recent Developments in the Identification of Antimicrobial Agents.

The marine ecosystem is the less explored, biologically diverse, and vastest resource to discover novel antimicrobial agents. In recent decades' antimicrobial drugs are losing their effectiveness due to the growing resistance among pathogens, which causes diseases to have considerable death rates across the globe. Therefore, there is a need for the discovery of new antibacterials that can reach the market. There is a gradual growth of compounds from marine sources which are entering the clinical trials. Thus, the prominence of marine natural products in the field of drug design and discovery across the academia and pharmaceutical industry is gaining attention. Herein, the present review covers nearly 200 marine based antimicrobial agents of 11 structural classes discovered from the year 2010 to 2022. All the discussed compounds have exhibited medium to high antimicrobial activity in inhibiting various microorganisms.

Microwave- and Ultrasound-Assisted Extraction of Cucurbitane-Type Triterpenoids from Momordica charantia L. Cultivars and Their Antiproliferative Effect on SAS Human Oral Cancer Cells.

Cucurbitane-type triterpenoids are a major class of bioactive compounds present in bitter melon. In the present study, six different cultivars of bitter melon were extracted by using microwave- or ultrasound-assisted techniques to identify the prominent method that can extract the majority of cucurbitane-type triterpenoids. A UHPLC-MS/MS (ultra-high-performance liquid chromatography tandem mass spectrometry) system was used for the identification and quantification of ten cucurbitane-type triterpenoids. The results suggest that the use of microwave-assisted extraction on cultivars 4 and 5 produced higher amounts of the selected cucurbitane-type triterpenoids. The interpretation of principal component analysis also identified that cultivar 4 is significantly different from the others in which the compounds 3ß,7ß,25-trihydroxycucurbita-5,23(E)-dien-19-al and momordicine I were found in higher quantities. Upon further evaluation, it was also identified that these two triterpenoids can act as antiproliferative agents due to their effects on SAS human oral cancer cell lines.

Medicinal plants as a potential source of Phosphodiesterase-5 inhibitors: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence and distress caused by erectile dysfunction (ED) to both male and female partners are increasing at a steady rate. ED has now become the most treated sexual disorder for men among young and old age groups due to varying physical and psychological factors. The treatment with synthetic Phosphodiesterase-5 (PDE5) inhibitors are cost-effective but due to adverse effects such as priapism, loss of vision, heart attack and syncope, the daily life patterns of these patients are distressed and hence the need for alternative medicaments or sources are of utmost important. Therefore, the exploration of medicinal plants as PDE5 inhibitors will be worthwhile in tackling the problems as many plant extracts and fractions have been long used as aphrodisiacs and sexual stimulants which may be found to be active against PDE5 enzyme. AIM OF THE STUDY: To provide a review on the different medicinal herbs traditionally used as natural aphrodisiacs, libido or sexual enhancers which are proven for their PDE5 inhibitory effect. MATERIALS AND METHODS: Ethnobotanical and scientific information was procured, reviewed and compiled from the literature search of electronic databases and search engines. RESULTS: A total of 97 medicinal plants exhibiting PDE5 inhibitory effect are reviewed in this paper which is supported by preclinical experimental evidence. Among them, 77 plants have been selected according to their traditional and ethnobotanical uses as aphrodisiacs and the rest are screened according to their effectiveness against predisposing factors responsible for ED and sexual dysfunction such as diabetes and hypertension or due to the presence of phytochemicals having structural similarity towards the identified natural PDE5 inhibitors. In addition, sixteen alkaloids, sixty-one phenolics and eight polycyclic aromatic hydrocarbons have been isolated or identified from active extracts or fractions that are exhibiting PDE5 inhibitory activity. Among them, isoflavones and biflavones are the major active constituents responsible for action, where the presence of prenyl group for isoflavones; and the methoxy group at C-5 position of flavones are considered essential for the inhibitory effect. However, the prenylated flavonol glycoside, Icariin and Icariside II isolated from Epimedium brevicornum Maxim (hory goat weed) are the most effective inhibitor, till date from natural sources. Traditional medicines or formulations containing extracts of Ginkgo biloba L., Kaempferia parviflora Wall. ex Baker, Clerodendrum colebrookianum Walp., Eurycoma longifolia Jack and Vitis vinifera L. are also found to be inhibitors of PDE5 enzyme. CONCLUSION: The review suggests and supports the rational use of traditional medicines that can be further studied for the development of potential PDE5 inhibitors. Many traditional medicines are still used in various regions of Africa, Asia and South America that are poorly characterized and experimented. Despite the availability of a vast majority of traditional formulations as aphrodisiacs or sexual stimulants, there exists a need for systemic evaluation on the efficacy as well as the mechanism of action of the herbal constituents for the identification of novel chemical moieties that can be further developed for maximum efficacy.

Aphrodisiac properties of hydro-alcoholic extract of Cassia auriculata flower in male rats.

Cassia auriculata is a commonly found plant in Asia, widely used in Ayurveda and Siddha medicines as a tonic, astringent and in general for diabetes. Herbal tea made from this plant has been marketed as a product for restoring sexual vitality, to increase sperm count and counteract ejaculatory disorders. However, the scientific evidences are scarce to prove this concept. Here, we examined the effect of hydro-alcoholic extract obtained from C. auriculata flower upon the expression of male Wistar albino rat's sexual behaviour. Sildenafil was used as a positive control. Penile erection index (PEI), mount latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), ejaculation frequency (EF) and post-ejaculatory interval (PEjI) were recorded for days 0, 7, 14 and 28 and also after the withdrawal of the treatment on days 7 and 15. Significant reduction in ML, IL and PEjI, and increment in EL, PEI, MF, IF and EF were observed (p < 0.05, <0.01). However, neither extract nor sildenafil sustains the effect after withdrawal of the treatment. The present finding demonstrates the aphrodisiac potential of hydro-alcoholic extract of C. auriculata flower in vivo and lends support to the traditional utilisation as a sexual stimulating agent.

Facile, environmentally benign and scalable approach to produce pristine few layers graphene suitable for preparing biocompatible polymer nanocomposites.

The success of developing graphene based biomaterials depends on its ease of synthesis, use of environmentally benign methods and low toxicity of the chemicals involved as well as biocompatibility of the final products/devices. We report, herein, a simple, scalable and safe method to produce defect free few layers graphene using naturally available phenolics i.e. curcumin/tetrahydrocurcumin/quercetin, as solid-phase exfoliating agents with a productivity of ∼45 g/batch (D/G ≤ 0.54 and D/D' ≤ 1.23). The production method can also be employed in liquid-phase using a ball mill (20 g/batch, D/G ≤ 0.23 and D/D' ≤ 1.12) and a sand grinder (10 g/batch, D/G ≤ 0.11 and D/D∼ ≤ 0.78). The combined effect of π-π interaction and charge transfer (from curcumin to graphene) is postulated to be the driving force for efficient exfoliation of graphite. The yielded graphene was mixed with the natural rubber (NR) latex to produce thin film nanocomposites, which show superior tensile strength with low modulus and no loss of % elongation at break. In-vitro and in-vivo investigations demonstrate that the prepared nanocomposite is biocompatible. This approach could be useful for the production of materials suitable in products (gloves/condoms/catheters), which come in contact with body parts/body fluids.

Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. ß-Amyloid (Aß) has been proposed to play a role in the pathogenesis of AD. Deposits of insoluble Aß are found in the brains of patients with AD and are one of the pathological hallmarks of the disease, but the underlying signaling pathways are poorly understood. In order to develop antidementia agents with potential therapeutic value, we examined the inhibitory effect of the Nelumbo nucifera seed embryo extracts on to the aggregated amyloid ß peptide (agg Aß1-40)-induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for AD. In the present study, seed embryos of N. nucifera were extracted with 70% methanol in water and then separated into hexane, ethyl acetate, n-butanol, and water layers. Among them, only the n-butanol layer showed strong activity and was therefore subjected to separation on Sephadex LH-20 chromatography. Two fractions showing potent activity were found to significantly inhibit Aß1-40 toxicity on dPC-12 cells in increasing order of concentration (10-50 µg/mL). Further purification and characterization of these active fractions identified them to be flavonoids such as rutin, orientin, isoorientin, isoquercetrin, and hyperoside. 2,2-Diphenyl-1-picrylhydrazyl hydrate scavenging activity of the extracts was also carried out to ascertain the possible mechanism of the activity.

Poly(glycerol sebacate)-Based Polyester-Polyether Copolymers and Their Semi-Interpenetrated Networks with Thermoplastic Poly(ester-ether) Elastomers: Preparation and Properties.

Poly(glycerol sebacate) (PGS), produced from renewable monomers such as sebacic acid and glycerol, has been explored extensively for various biomedical applications. However, relatively less attention has been paid to explore PGS as sustainable materials in applications such as elastomers and rigid plastics, primarily because of serious deficiencies in physical properties of PGS. Here, we present two new approaches for enhancing the properties of PGS; (i) synthesizing block copolymers of PGS with poly(tetramethylene oxide)glycol (PTMO) and (ii) preparing a blend of PGS-b-PTMO with a poly(ester-ether) thermoplastic elastomer. The consequence of molar ratio (hard and soft segments) and M n of soft segment on tensile properties of the material was investigated. The PGS-b-PTMO with 25:75 mole ratios of hard and soft segments and having a medium M n soft segment (5350 g mol-1) exhibits an appreciable increase in percentage of elongation that is from 32% for PGS to 737%. Blends of PGS-b-PTMO and a thermoplastic polyester elastomer, Hytrel 3078, form a semi-interpenetrated polymer network, which exhibits increased tensile strength to 2.11 MPa and percentage of elongation to 2574. An elongation of such magnitude is unprecedented in the literature for predominantly aliphatic polyesters and demonstrates that the simple polyester can be tailored for superior performance.

Thermally conductive thin films derived from defect free graphene-natural rubber latex nanocomposite: Preparation and properties.

Commercially useful rubber products viz. gloves, condoms, tyres, and rubber hoses used in high temperature environments, etc., require efficient thermal conductivity, which increases the lifetime of these products. Graphene can fetch this property, if it is effectively incorporated into the rubber matrix. The great challenge in preparing graphene-rubber nanocomposites is formulating a scalable method to produce defect free graphene and its homogeneous dispersion into polymer matrices through an aqueous medium. Here, we used a simple method to produce defect free few layer (2-5) graphene, which can be easily dispersed into natural rubber (NR) latex without adversely affecting its colloidal stability. The resulting new composite showed large increase in thermal conductivity (480-980%) along with 40% increase in tensile properties and 60% improvement in electrical conductivity. This study provides a novel and generalized approach for the preparation of graphene based thermally conductive rubber nanocomposites.

Transformation of proanthocyanidin A2 to its isomers under different physiological pH conditions and common cell culture medium.

Proanthocyanidins constitute an important class of polyphenols ubiquitously found in plants. They have been extensively studied for their antioxidant capacity and bioactivity in vitro and in animal models. However, their stability under different pH conditions and in cell culture medium has not been well documented. In the present study, it was observed that proanthocyanidin A2 (PA2) was relatively more stable in acidic condition than in weak alkaline condition. PA2 was also quite unstable in basal-Dulbecco's Modified Eagle medium (b-DMEM medium) at 37 °C. The addition of PA2 to the cell culture medium accelerated its epimerization with a half-life of <15 min, and ethylenediaminetetraacetic acid (EDTA) could not stop the reaction. The results also demonstrated that the major isomers transformed in the weak alkaline condition or cell culture medium at 37 °C were identified as epicatechin-(4ß→8; 2ß→O→7)-ent-catechin (proanthocyanidin A4) and epicatechin-(4ß→6; 2ß→O→7)-ent-catechin. The rates of transformation were dependent on the pH or the components of the medium. Therefore, the results obtained for PA2 in the cell culture bioassays, which were usually carried out for 24 h, might not represent the true activity of the original PA2. The stability and transformation of PA2 should be considered when the bioactivity of PA2 is evaluated in a given cell culture system.