Molecular Docking and Network Pharmacology Interaction Analysis of Gingko Biloba (EGB761) Extract with Dual Target Inhibitory Mechanism in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative dementia affecting people in their later years of life. The AD prevalence rate has significantly increased due to a lack of early detection technology and low therapeutic efficacy. Despite recent scientific advances, some aspects of AD pathological targets still require special attention. Certain traditionally consumed phytocompounds have been used for thousands of years to treat such pathologies. The standard extract of Gingko biloba (EGB761) is a combination of 13 macro phyto-compounds and various other micro phytocompounds that have shown greater therapeutic potential against the pathology of AD. OBJECTIVE: Strong physiological evidence of cognitive health preservation has been observed in elderly people who keep an active lifestyle. According to some theories, consuming certain medicinal extracts helps build cognitive reserve. We outline the research employing EGB761 as a dual target for AD. METHODS: This study investigates various inhibitory targets against AD using computational approaches such as molecular docking, network pharmacology, ADMET (full form), and bioactivity prediction of the selected compounds. RESULTS: After interaction studies were done for all the phytoconstituents of EGB761, it was concluded that all four of the phytocompounds (kaempferol, isorhamnetin, quercetin, and ginkgotoxin) showed the maximum inhibitory activity against acetylcholinesterase (AChE) and GSK3ß. CONCLUSION: The highly active phytocompounds of EGB761, especially quercetin, kaempferol, and isorhamnetin, have better activity against AChE and GSK3ß than its reported synthetic drug, according to molecular docking and network pharmacology research. These compounds may act on multiple targets in the protein network of AD. The AChE theory was primarily responsible for EGB761's therapeutic efficacy in treating AD.

Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.

The vast use of corticosteroids (CCSs) globally has led to an increase in CCS-induced neuropsychiatric disorders (NPDs), a very common manifestation in patients after CCS consumption. These neuropsychiatric disorders range from depression, insomnia, and bipolar disorders to panic attacks, overt psychosis, and many other cognitive changes in such subjects. Though their therapeutic importance in treating and improving many clinical symptoms overrides the complications that arise after their consumption, still, there has been an alarming rise in NPD cases in recent years, and they are seen as the greatest public health challenge globally; therefore, these potential side effects cannot be ignored. It has also been observed that many of the neuronal functional activities are regulated and controlled by genomic variants with epigenetic factors (DNA methylation, non-coding RNA, and histone modeling, etc.), and any alterations in these regulatory mechanisms affect normal cerebral development and functioning. This study explores a general overview of emerging concerns of CCS-induced NPDs, the effective molecular biology approaches that can revitalize NPD therapy in an extremely specialized, reliable, and effective manner, and the possible gene-editing-based therapeutic strategies to either prevent or cure NPDs in the future.

Natural sources and encapsulating materials for probiotics delivery systems: Recent applications and challenges in functional food development.

Probiotics are known as the live microorganisms which upon adequate administration elicit a health beneficial response inside the host by decreasing the luminal pH, eliminating the pathogenic bacteria in the gut as well as producing short chain fatty acids (SCFA). With advancements in research; probiotics have been explored as potential ingredients in foods. However, their use and applications in food industry have been limited due to restrictions of maintaining the viability of probiotic cells and targeting the successful delivery to gut. Encapsulation techniques have significant influence on increasing the viability rates of probiotic cells with the successful delivery of cells to the target site. Moreover, encapsulating techniques also prevent the live cells from harsh physiological conditions of gut. This review discusses several encapsulating techniques as well as materials derived from natural sources and nutraceutical compounds. In addition to this, this paper also comprehensively discusses the factors affecting the probiotics viability and evaluation of successful release and survival of probiotics under simulated gastric, intestinal conditions as well as bile, acid tolerant conditions. Lastly applications and challenges of using encapsulated bacteria in food industry for the development of novel functional foods have also been discussed in detail too. Future studies must include investigating the use of encapsulated bacterial formulations in in-vivo models for effective health beneficial properties as well as exploring the mechanisms behind the successful release of these formulations in gut, hence helping us to understand the encapsulation of probiotic cells in a meticulous manner.

Utility of Chitra-HASi Granules in Cystic Defects of the Maxillofacial Region: A Pilot Study.

BACKGROUND: Cystic defects that are critical sized or larger require bone replacement strategies. However, due to inherent disadvantages of the various types of grafts, none of the available materials are best suited for these defects. Among the alloplastic materials, hydroxyapatite (HA)-based grafts are the most popular, due to their osteoconductive nature and resemblance to mineral bone. The aim of the study was to assess the utility of the novel material "Chitra-HASi" as a bone substitute in the maxillofacial region. MATERIALS AND METHODS: In a single-arm, prospective study, patients with radicular and dentigerous cysts were included and the minimum defect size was standardized at 20 × 20 mm or above. The Chitra-HASi material was developed by a wet precipitation technique and adopted for use following multiple in vitro and in vivo studies, confirming its safety and biocompatibility profile. All cysts underwent enucleation, followed by peripheral ostectomy and apicectomy of the teeth involved. The HASi graft was packed inside the cystic defect in a granular form and covered with a mucoperiosteal flap. Panoramic radiographs were taken preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: Twenty-three patients were included in the study, of which only 10 patients could be followed up for 12 months after graft placement. The mean preoperative bone density was found to be 14.9% ± 4.97 (standard deviation), whereas the postoperative 3-month, 6-month, and 12-month densities had a mean difference of -11.3%, -22.9%, and -37.3%, respectively, and the differences were statistically significant. Minor complications such as sinus formation (n = 7) and extrusion of granules (n = 4) were noted, which were managed conservatively. Only two patients required graft removal secondary to infection, leading to a persistent sinus tract. CONCLUSION: The results of the study suggest that Chitra-HASi granules show potential as an alternative to other bone substitutes. The addition of silica to the porous HA material offers superior strength characteristics and needs long-term evaluation to assess its stability in large cystic defects.

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries.

Apocynin (APO) is a known multi-enzymatic complexed compound, employed as a viable NADPH oxidase (NOX) inhibitor, extensively used in both traditional and modern-day therapeutic strategies to combat neuronal disorders. However, its therapeutic efficacy is limited by lower solubility and lesser bioavailability; thus, a suitable nanocarrier system to overcome such limitations is needed. The present study is designed to fabricate APO-loaded polymeric nanoparticles (APO-NPs) to enhance its therapeutic efficacy and sustainability in the biological system. The optimized APO NPs in the study exhibited 103.6 ± 6.8 nm and -13.7 ± 0.43 mV of particle size and zeta potential, respectively, along with further confirmation by TEM. In addition, the antioxidant (AO) abilities quantified by DPPH and nitric oxide scavenging assays exhibited comparatively higher AO potential of APO-NPs than APO alone. An in-vitro release profile displayed a linear diffusion pattern of zero order kinetics for APO from the NPs, followed by its cytotoxicity evaluation on the PC12 cell line, which revealed minimal toxicity with higher cell viability, even after treatment with a stress inducer (H2O2). The stability of APO-NPs after six months showed minimal AO decline in comparison to APO only, indicating that the designed nano-formulation enhanced therapeutic efficacy for modulating NOX-mediated ROS generation.

Anti-Inflammatory and Anti-Arthritic Potential of Standardized Extract of Clerodendrum serratum (L.) Moon.

Aims: Scientific biological evaluation of standardized extracts is becoming one of the central needs for the globalization of customary medication in current times. And to validate the presence of active constituents in crude medicinal extracts, analytical techniques like HPLC and HPTLC are the most suitable authentication systems. In the current study we aimed to standardize and evaluate Clerodendrum serratum (L.) Moon (Verbenaceae). For its unique anti-inflammatory and anti-arthritic properties. Evaluation and analysis of the plant, therefore, offers a new platform for the development of the herbal drug and could prove to be a safe and cost effective treatment for arthritis management. Methods: The aqueous extract of C. serratum, a common plant in the Southeastern Asian region, was used for phytochemical investigation and standardization by HPTLC and HPLC. The standardized HPLC method was further validated by using ICH guidelines. The standardized extract was investigated for anti-inflammatory and anti-arthritic activity. Complete Freund's adjuvant (CFA) model was performed to evaluate the activity. Paw diameter, joint diameter, arthritic score, and body weight was accepted as a parameter for the evaluation of biological activity. Results: HPTLC method revealed the presence of ursolic acid with an Rf value of 0.38 and the amount quantified was 0.03% w/w. The presence of the bioactive phytochemical was further analyzed and confirmed by HPLC for which the validation was done successfully in accordance with ICH guidelines. The assay content for ursolic acid was found to be 0.059% with relative standard deviation (RSD) <2.5% for specificity and precision with spike recovery between 95-110%. The anti-arthritic activity of aqueous extract exhibited COX-2 and TNF-α inhibition as observed in various parameters like paw edema, arthritic index, and joint diameter. Plant extract showed reclamation of arthritis in regard to body weight, arthritic score, paw edema, and joint diameter. The extract showed significant results for TNF-α and COX-2(p < 0.0001). The plant extract also exhibited in-vitro anti-inflammatory activity. Conclusion: The current study established the scientific basis of ethnomedicinal use of the plant for anti-inflammatory purposes and the management of arthritis and can also be used for quality control purposes.

Current and Future molecular mechanism in Inflammation and Arthritis.

Inflammation is an immune response of the human body but excessive inflammation is taken as a major factor in the development of many diseases including autoimmune disorders, cancer and nerve disorders etc. In this regards the need is to suppress the inflammatory response. Suppression of extra or imperfect inflammatory response is not a big deal provided there is an exact knowledge of particular target in the body. Recent advancements in Pharmacological aspect made the therapy with improved outcomes in number of patients. Anticytokine therapy might be one of the important and novel approaches for inflammation and Arthritis. This can be achieved only when we go through the pathophysiology of expression and identification of mediators. Let's take an example of cytokine like interleukins (IL), chemokines, interferons (INF), tumor necrosis factors (TNF-α), growth factors, and colony stimulating factors) release pathway which is a major signalling protein in inflammatory response. In the present study we have reviewed the recent pharmacological therapeutic advancement, inflammatory mediators, receptors, and major signalling pathways. Such information will not only provide the idea about the mechanism of action of Pharmaceuticals and molecular targets but also it provides a new aspect for drug designing and new corrective approaches in existing clinical medicines. This study will be a source of good information for the researchers working in the area of drug designing and molecular Pharmacology especially in anti-inflammatory and anti arthritic medicines for target based therapy.

Nicotine Addiction: Neurobiology and Mechanism.

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

Nutraceuticals Inspiring the Current Therapy for Lifestyle Diseases.

Nutraceuticals are the pharmaceutically blended products that possess both nutritional as well as the medicinal value. Such a product is designed to improve the physical health, fight against day-to-day challenges such as stress, increase longevity, etc. Nowadays, emphasis is given to those herbs which are used as food and medicine due to its greater acceptance. Due to dynamic action, the popularity of nutraceuticals among people as well as healthcare providers has been increased over medicines and health supplements. This review documents herbs with a wide variety of therapeutic values such as immunity booster, antidiabetic, anticancer, antimicrobial, and gastroprotective. These herbs could be better options to formulate as nutraceuticals. Several nutraceuticals are described based on their availability as food, chemical nature, and mechanism of action.

Gastroprotective mechanism of Paederia foetida Linn. (Rubiaceae)--a popular edible plant used by the tribal community of North-East India.

BACKGROUND: The objective of the present study is to evaluate the gastroprotective activity of Paederia foetida L. leaf for gastric ulcer. METHODS: The methanol extract of P. foetida L. leaves at two different dose levels was investigated for gastroprotective potential by using Indomethacin-pylorus ligation, alcohol induced and water immersion stress induced model in rats. In vitro DPPH* radical scavenging activity and western blot analysis of stomach tissue from pylorus ligatures rats were also carried out. HPTLC analysis was done to understand the phyto-pharmacological relationship. RESULTS: Methanol extract at a dose level of 100 mg/kg and 200 mg/kg body weight showed 72 and 78% ulcer protection when compared to negative control whereas reference drug shown 82% protection in Indomethacin-pylorus ligation model. Further, methanol extract also showed protective effect against 70% v/v ethanol and stress induced gastric ulcer model. About 84% protection as compared to cimetidine (85%) was seen in western blot analysis of stomach tissue from pylorus ligatures rats. HPTLC analysis of methanol extract of P. foetida L. confirmed the presence of ß-sitosterol. In DPPH* radical scavenging activity, the IC50 value was observed to be 43.52 µg/ml. CONCLUSIONS: These observations established the traditional claim and thus Paederia foetida could be a potent gastroprotective agent for use in future. The gastroprotective activity might be mediated by the Nrf2 mediated antioxidant and anti secretory effects.