Current Drug Research Reviews - Volume 16, Issue 2, 2024

The study of transporter proteins is key to understanding the mechanism behind multidrug resistance and drug-drug interactions causing severe side effects. While ATP-binding transporters are well-studied, solute carriers illustrate an understudied family with a high number of orphan proteins. To study these transporters, in silico methods can be used to shed light on the basic molecular machinery by studying protein-ligand interactions. Nowadays, computational methods are an integral part of the drug discovery and development process. In this short review, computational approaches, such as machine learning, are discussed, which try to tackle interactions between transport proteins and certain compounds to locate target proteins. Furthermore, a few cases of selected members of the ATP binding transporter and solute carrier family are covered, which are of high interest in clinical drug interaction studies, especially for regulatory agencies. The strengths and limitations of ligand-based and structure-based methods are discussed to highlight their applicability for different studies. Furthermore, the combination of multiple approaches can improve the information obtained to find crucial amino acids that explain important interactions of protein-ligand complexes in more detail. This allows the design of drug candidates with increased activity towards a target protein, which further helps to support future synthetic efforts.

The Endocannabinoid System (ECS) is a well-studied system that influences a variety of physiological activities. It is evident that the ECS plays a significant role in metabolic activities and also has some neuroprotective properties. In this review, we emphasize several plant-derived cannabinoids such as β-caryophyllene (BCP), Cannabichromene (CBC), Cannabigerol (CBG), Cannabidiol (CBD), and Cannabinol (CBN), which are known to have distinctive modulation abilities of ECS. In Alzheimer's disease (AD), the activation of ECS may provide neuroprotection by modulating certain neuronal circuitry pathways through complex molecular cascades. The present article also discusses the implications of cannabinoid receptors (CB1 and CB2) as well as cannabinoid enzymes (FAAH and MAGL) modulators in AD. Specifically, CBR1 or CB2R modulations result in reduced inflammatory cytokines such as IL-2 and IL-6, as well as a reduction in microglial activation, which contribute to an inflammatory response in neurons. Furthermore, naturally occurring cannabinoid metabolic enzymes (FAAH and MAGL) inhibit the NLRP3 inflammasome complex, which may offer significant neuroprotection. In this review, we explored the multi-targeted neuroprotective properties of phytocannabinoids and their possible modulations, which could offer significant benefits in limiting AD.

Nutraceuticals are the foods that are used to prevent and cure diseases. Food and nutrients are essential for the body's normal function and aid in the maintenance of an individual's health and prevent various diseases. Nutraceuticals are medicinal foods that aid in the maintenance of health, the enhancement of immunity, and the prevention and treatment of specific diseases. The markets of nutraceuticals are one of the fastest-growing industry segments. The prime reason for this accelerated market growth lies in the fact that nutraceuticals are low cost, can prevent diseases to occur, hence, can save the health care cost, have more nutritional value, and many others. Nutraceuticals can be classified on different foundations based on what they promise, natural sources, and nutraceutical food available in the market. This article will discuss those classifications in detail along with the role of nutraceuticals in lifestyle diseases, regulations, market trends, and prospects of nutraceuticals. The article will also highlight the concern areas which play as the limiting factor in the nutraceuticals industry growth like lack of quality control, lack of data on its working, and many other things.

COVID-19 is an RNA virus that attacks the targeting organs, which express angiotensin- converting enzyme-2 (ACE-2), such as the lungs, heart, renal system, and gastrointestinal tract. The virus that enters the cell by endocytosis triggers ROS production within the confines of endosomes via a NOX-2 containing NADPH-oxidase. Various isoforms of NADPH oxidase are expressed in airways and alveolar epithelial cells, endothelial and vascular smooth muscle cells, and inflammatory cells, such as alveolar macrophages, monocytes, neutrophils, and Tlymphocytes. The key NOX isoform expressed in macrophages and neutrophils is the NOX-2 oxidase, whereas, in airways and alveolar epithelial cells, it appears to be NOX-1 and NOX-2. The respiratory RNA viruses induce NOX-2-mediated ROS production in the endosomes of alveolar macrophages. The mitochondrial and NADPH oxidase (NOX) generated ROS can enhance TGF-β signaling to promote fibrosis of the lungs. The endothelium-derived ROS and platelet-derived ROS, due to activation of the NADPH-oxidase enzyme, play a crucial role in platelet activation. It has been observed that NOX-2 is generally activated in COVID-19 patients. The post-COVID complications like pulmonary fibrosis and platelet aggregation may be due to the activation of NOX-2. NOX-2 inhibitors may be a useful drug candidate to prevent COVID-19 complications like pulmonary fibrosis and platelet aggregation.

Skin cancer is one of the deadly diseases of the skin characterized by pain and uncontrolled growth of cells. The pathogenesis of skin cancer involves the uncontrolled division of abnormal cells in the part of the body affected by an accumulation of genome variation over the course of a lifetime. The incidence of skin cancer has been increasing all over the world and has been reported more in old-aged persons. Furthermore, aging plays a vital role in promoting malignancy. Cancer necessitates lifelong administration of drugs to maintain the quality of life. The major challenge of treatment is the side effects associated with these drugs. Novel and targeted approaches are now formulated to explore as an alternative measure to treat cancer. The current review summarizes the pathogenesis of cancer and its treatment strategies. These approaches are discussed with regard to the drugs, mechanism of action, causative factors, distribution of cancer, mortality rate, and treatment strategies.

Background: Nigella sativa (N. sativa), commonly known as black seed or black cumin, belongs to the family Ranunculaceae. It contains several phytoconstituents, Thymoquinone (TQ), thymol, thymohydroquinone, carvacrol, and dithymoquinone. TQ is the main phytoconstituent present in N. sativa that is used as an herbal compound, and it is widely used as an antihypertensive, liver tonic, diuretic, digestive, anti-diarrheal, appetite stimulant, analgesic, and antibacterial agent, and in skin disorders. Objective: The study focused on collecting data on the therapeutic or pharmacological activities of TQ present in N. sativa seed. Methods: Antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, hepato-protective, renal protective, and antioxidant properties of TQ have been studied by various scientists. Conclusion: TQ seems to have a variety of consequences on how infected cells behave at the cellular level.

Background: Pueraria lobata is an important herbal medicine of Fabaceae family that has been clinically used in Traditional Chinese Medicine to counteract human disorders and associated secondary complications. Kakkalide also called irisolidone 7-xylosylglucoside is an isoflavonoid of Puerariae flos, Pueraria lobata and Flos Puerariae. Moreover, Kakkalide has a wide range of bioactivities in medicine. Methods: Biological potential of kakkalide was investigated in the present work through scientific data analysis of different scientific research work on kakkalide in order to know its therapeutic potential in medicine. Scientific data on Pueraria lobata were collected and analyzed in the present work. All the scientific data were collected from Google, Google Scholar, Scopus, and Science Direct in the present work. Results: Scientific data analysis of kakkalide revealed its biological importance and therapeutic potential in medicine. The present investigation signified kakkalide's effectiveness in inflammatory diseases, prostaglandin E2 production, liver complication, gastric injury, alcoholism, insulinresistant endothelial dysfunction, aldose reductase enzyme, hyperlipidemia, estrogenic activity, and stroke. In addition, the bioavailability of kakkalide was also discussed in the present paper. Present work also revealed the significance of analytical techniques for the separation, isolation and identification of kakkalide in different biological and non-biological samples. Conclusion: Present paper signified the health-beneficial aspects of kakkalide in medicine.

Flavonoids are a family of secondary metabolites found in plants and fungi that exhibit strong antioxidant properties and low toxicity, making them potential candidates for medicinal use. Quercetin, a flavonoid present in various plant-based foods, has gained attention for its numerous biological benefits, including anti-inflammatory, anti-fibrosis, and antioxidant properties. The ocular surface research community has recently focused on quercetin's therapeutic potential for managing ocular diseases, such as dry eye, keratoconus, corneal inflammation, and neovascularization. In this paper, we discuss the role of quercetin for ocular disease prevention, highlighting its fundamental characteristics, common biological properties, and recent applications. By reviewing the latest research conducted in the last 10 years which was focused on novel herbal formulations for ocular diseases, we aim to provide insights into the role of quercetin in managing ocular diseases and offer perspectives on its potential as a therapeutic agent.

Background: Multiple sclerosis (MS), a chronic inflammatory disorder, affects the central nervous system via myelin degradation. The cause of MS is not fully known, but during recent years, our knowledge has deepened significantly regarding the different aspects of MS, including etiology, molecular pathophysiology, diagnosis and therapeutic options. Myelin basic protein (MBP) is the main myelin protein that accounts for maintaining the stability of the myelin sheath. Recent evidence has revealed that MBP citrullination or deamination, which is catalyzed by Ca²⁺ dependent peptidyl arginine deiminase (PAD) enzyme leads to the reduction of positive charge, and subsequently proteolytic cleavage of MBP. The overexpression of PAD2 in the brains of MS patients plays an essential role in new epitope formation and progression of the autoimmune disorder. Some drugs have recently entered phase III clinical trials with promising efficacy and will probably obtain approval in the near future. As different therapeutic platforms develop, finding an optimal treatment for each individual patient will be more challenging. Aims: This review provides a comprehensive insight into MS with a focus on its pathogenesis and recent advances in diagnostic methods and its present and upcoming treatment modalities. Conclusion: MS therapy alters quickly as research findings and therapeutic options surrounding MS expand. McDonald's guidelines have created different criteria for MS diagnosis. In recent years, ever-growing interest in the development of PAD inhibitors has led to the generation of many reversible and irreversible PAD inhibitors against the disease with satisfactory therapeutic outcomes.

Sunscreens cover the big market ratio in terms of cosmetic applications, but the therapeutic necessity of sunscreen still needs to be uncovered in the clinical context. Clinically, sunscreens are being employed more often nowadays as a result of the rising consequences of skin malignancies and the photodamaging effects of UV radiation. Sunscreens are essential to prevent aging by shielding the skin from the harmful effects of ultraviolet (UV) radiation. Over the recent decades, there has been a significant evolution in the usage of sunscreens as photo protectants. The demand for sunscreen formulations will inevitably rise as more people become aware of the protection that sunscreens provide against tanning, photoaging, non-melanoma skin cancers, premalignant skin lesions, and skin melanomas. The novel contemporary formulation techniques are also beneficial in enhancing the product's aesthetic look and quality. Recently, regulatory agencies have also started paying attention to the regulation of the clinical application, efficacy, and safety parameters related to sunscreen. This review underlines the pathophysiological response of UV exposure with the therapeutic applications of sunscreen in various dermatological conditions and the recent formulation advancements in the development of sunscreen.

Background: Herbal medicines have been used for the preparation of numerous pharmaceutical products for the treatment of human disorders. Plant-derived products have been used in medicine, nutraceuticals, perfumery, beverages, and cosmetics industries for different purposes. Herbal medicines are mainly derived from different parts of plant materials. Phellodendron bark has been widely known as one of the fundamental herbs of traditional Chinese medicine. Phellodendron bark contains phellodendrine as a main active phytochemical. Phellodendrine ((7S,13aS)-3,10-dimethoxy-7-methyl-6,8,13,13atetrahydro-5H-isoquinolino[2,1-b]isoquinolin-7- ium-2,11-diol), is a quaternary ammonium alkaloid. Methods: This present study aimed to investigate the biological potential and therapeutic effectiveness of phellodendrine in medicine through scientific data analysis of different research works on phellodendrine. The therapeutic value of phellodendrine was analyzed in the present work through scientific data available in Google, Google Scholar, ScienceDirect, and PubMed. All the scientific data on phellodendrine were collected from these databases using the terms herbal drugs and phellodendrine. Pharmacological and analytical data of phellodendrine were analyzed in the present work in order to know the medicinal importance of phellodendrine. Results: Scientific data analysis of phellodendrine in the present work signified the biological importance of phellodendrine in medicine. Phellodendrine has numerous beneficial aspects in medicine due to its potential benefits in ulcerative colitis, inflammation, pancreatic cancer, nephritis, immune response, acetylcholinesterase activity, psoriasis, arthritis, atopic dermatitis, and oxidative stress. However, it also has significant effects on eicosanoid generation, neuraminidase-1, inflammasome generation, cytochrome p450, taste receptors, and hepatic gluconeogenesis. Furthermore, scientific data has indicated the presence of phellodendrine in different natural sources, including Phellodendri cortex. Analytical data on phellodendrines has signified their importance in the isolation and separation of pure phytochemicals in medicine. Pharmacokinetic parameters have highlighted the tissue distribution of phellodendrine in different tissue of human beings and higher animals. Conclusion: In the present work, scientific data analysis has indicated the biological importance, pharmacological activities, and analytical aspects of phellodendrine in medicine.

Introduction: Dysmenorrhea is the most common periodic pain, which affects more than 50% of women with regular menstruation. Fenugreek is one of the medicinal plants with analgesic properties. This study aimed to determine the effect of fenugreek application in the severity of dysmenorrhea and its side effects in women with dysmenorrhea. PICO: Population: women with dysmenorrhea; Intervention: fenugreek; Comparison: control groups; and Outcome: reduction in the severity of dysmenorrhea and its side effects. Methods: English database (PubMed, Cochrane Library, Scopus, and Web of Science) and Persian database [SID (Scientific Information Database) and Magiran] were used for research until February 11, 2023, using the keywords “Dysmenorrhea [Mesh],” “Foenum [Mesh],” “fenugreek [Mesh],” and “Trigonella [Mesh].” The reference list of the selected articles was also checked. The quality assessment was conducted through the Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0. The RevMan 5.3 software was used to analyze and report the data of the entered studies. Meta-analysis results were reported with the standardized mean difference (95% confidence interval). A subgroup analysis was performed based on the type of control groups. The quality of evidence was assessed using the GRADE approach. Results: After removing duplicates and ineligible cases, four articles were included in the systematic review out of the 1526 records obtained. The results showed that the pain intensity caused by primary dysmenorrhea decreased with fenugreek compared to placebo (pooled result SMD: -2.21; 95% CI: -3.26 to -1.17; Z: 4.17; p <0.001). There was no significant difference between fenugreek with mefenamic acid (SMD: 0.05; 95% CI: -0.57 to 0.67; Z: 0.17; p = 0.86) and fenugreek with Chandrasura churna (SMD: 0.06; 95% CI: -0.56 to 0.68; Z: 0.19; p = 0.85). Bias, in terms of incomplete outcome data and selective reporting, was low risk in all studies, and the available evidence was low quality according to the GRADE approach. Conclusion: The results showed that the effect of fenugreek on pain intensity in dysmenorrhea is highly uncertain. The true effect is likely to be substantially different from the estimate of effect. Regarding the importance of the health and quality of life of women of reproductive age and the low quality of evidence of the studies, clinical trials with stronger methodology are suggested in this field.

Introduction: Progress towards the 95-95-95 target among People Who Inject Drugs (PWID) with Human Immunodeficiency Virus (HIV) infection was considerably low. A behavioral approach, such as motivational interviewing (MI), has been recognized as an effective strategy for improving HIV treatment outcomes among PWID. Objective: This study aimed at assessing the impact of MI counselling to improve ARV initiation among HIV-positive PWID. Methods: A cohort design pilot study was performed, and participants were recruited using a convenience sampling technique. Participants were PWID with HIV who accessed healthcare facilities in two Indonesian cities. Selected participants were assigned to an intervention group and a control group. The intervention group followed MI counselling, while the control group received ART following the standard of care. The participants were assigned to each group based on their preferences. The data was collected between January 2018 and January 2019. Results: In total, 115 PWID with HIV participated in this study in the intervention (n = 30) and control (n = 85) groups. All but one intervention group's participants started ART, while 68/85 in the control group did so. Receiving MI counselling significantly contributed to ART initiation. In addition, the participants were followed-up until 12 months after ARV initiation. During this period, we found that similar proportions of participants in both groups discontinued the treatment, and only a small number achieved HIV viral suppression. Conclusion: The positive effect of MI counselling on ART initiation provides insight into the possibility of its wider implementation. Further studies are needed to gain a deeper understanding of MI counselling and its effect on other outcomes of the HIV treatment cascade.

Aim: The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns and pre- and post-menstrual symptoms in women aged 18-45 years. Background: COVID-19 vaccination was introduced to combat the dreadful impacts of human coronavirus infection. The two indigenously developed COVID-19 vaccines approved for use in India are COVISHIELD and COVAXIN. Objectives: To investigate the effects of COVID-19 vaccination on the menstrual cycle, pre- and post-menstrual symptoms and to establish the correlation with the type of vaccine received. Methods: Multi-centric observational study conducted in six institutes of national importance in different states of India over one year. A total of 5709 female participants fulfilling inclusion criteria were enrolled. Data about the impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on the menstrual cycle and its associated symptoms were obtained using all participants' online and offline interviews. Results: Of 5709 participants, 78.2% received COVISHIELD and 21.8% COVAXIN. Of the total 5709 participants, 333 (5.8%) developed post-vaccination menstrual disturbances, with 32.7% having frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleeding. A total of 301 participants noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of the menstrual cycle (p = 0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to the COVISHIELD (5.3%) group. A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in the COVISHIELD group (p = 0.031), with generalized weakness and body pains as the main complaints (p = 0.001). No significant difference was observed in the incidence of COVID-19 infection with these vaccines. No significant associations were observed when comparing menstrual abnormalities among those with COVID-19 infection (p > 0.05). Conclusion: COVISHIELD and COVAXIN vaccines were associated with menstrual cycle disturbances and pre-and post-menstrual symptoms in a small proportion of participants, with 94.7% having no change in the amount of bleeding during menstruation post-vaccination. The menstrual irregularities observed were significantly higher with the COVAXIN vaccine. Others: Further, long-term studies are required to confirm that the impact of COVID-19 vaccination on the menstrual cycle may be short-lasting, with no severe effects on women's menstrual health.