Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment.

Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.

Flavonoids, Isoflavonoids and others Bioactives for Insulin Sensitizations.

Diabetes is a chronic condition that has an impact on a huge part of the world. Both animals and humans have been demonstrated to benefit from natural goods, and organisms (animals, or microbes). In 2021, approximately 537 million adults (20-79 years) are living with diabetes, making it the one of the biggest cause of death worldwide. Various phytoconstituent preserved ß- cells activity helps to prevent the formation of diabetes problems. As a result, ß-cells mass and function are key pharmaceutical targets. The purpose of this review is to provide an overview of flavonoids' effects on pancreatic ß-cells. Flavonoids have been demonstrated to improve insulin release in cell lines of isolated pancreatic islets and diabetic animal models. Flavonoids are thought to protect ß-cells by inhibiting nuclear factor-κB (NF-κB) signaling, activating the phosphatidylinositol 3-kinase (PI3K) pathway, inhibiting nitric oxide production, and lowering reactive oxygen species levels. Flavonoids boost ß-cells secretory capacity by improving mitochondrial bioenergetic function and increasing insulin secretion pathways. Some of the bioactive phytoconstituents such as S-methyl cysteine sulfoxides stimulate insulin synthesis in the body and increase pancreatic output. The berberine increased insulin secretion in the HIT-T15 and Insulinoma 6 (MIN6) mouse cell line. Epigallocatechin-3-Gallate protects against toxicity accrued by cytokines, reactive oxygen species (ROS), and hyperglycemia. Quercetin has been proven to boost insulin production by Insulinoma 1 (INS-1) cells and also protect cell apoptosis. Overall flavonoids have beneficial effects on ß-cells by prevented their malfunctioning or degradation and improving synthesis or release of insulin from ß-cells.

Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.

Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.

An outlook on the target-based molecular mechanism of phytoconstituents as immunomodulators.

The immune system is one of the essential defense mechanisms. Immune system inadequacy increases the risk of infections and cancer diseases, whereas over-activation of the immune system causes allergies or autoimmune disorders. Immunomodulators have been used in the treatment of immune-related diseases. There is growing interest in using herbal medicines as multicomponent agents to modulate the complex immune system in immune-related diseases. Many therapeutic phytochemicals showed immunomodulatory effects by various mechanisms. This mechanism includes stimulation of lymphoid cell, phagocytosis, macrophage, and cellular immune function enhancement. In addition increased antigen-specific immunoglobulin production, total white cell count, and inhibition of TNF-α, IFN-γ, NF-kB, IL-2, IL-6, IL-1ß, and other cytokines that influenced the immune system. This review aims to overview, widely investigated plant-derived phytoconstituents by targeting cells to modulate cellular and humoral immunity in in vivo and in vitro. However, further high-quality research is needed to confirm the clinical efficacy of plant-based immunomodulators.

Role of Plant Bioactive as Diuretics: General Considerations and Mechanism of Diuresis.

BACKGROUND: Medicinal plants have been found beneficial in the control and therapy of many ailments as they contain bioactive compounds, and many of them are used as precursors in the biosynthesis of natural medicines. Diuretics are used as a primary treatment in patients with edema associated with liver cirrhosis and kidney diseases, hyperkalemia, hypertension, heart failure, or renal failure. Furthermore, they are also used to increase the excretion of sodium and reduce blood volume. Due to various adverse events associated with synthetic diuretics, there is a need to investigate alternate plant-based bioactive components that have effective diuretic activity with minimal side effects. OBJECTIVE: This review compiled the reported bioactive compounds from different plant sources along with their mechanisms of diuretic activity. METHODS: Different sources were used to collect information regarding herbal plants with therapeutic value as diuretics. These included published peer-reviewed journal articles, scholarly articles from StatPearls, and search engines like Google Scholar, PubMed, Scopus, Springer, ScienceDirect, Wiley, etc. Results: In this review, it was found that flavonoids like rutin, acacetin, naringenin, etc. showed significant diuretic activity in experimental models by various mechanisms, but mostly by blocking the sodium-potassium-chloride co-transporter, while some bioactive compounds showed diuretic actions via other mechanisms as well. CONCLUSION: Research on clinical trials of these isolated bioactive compounds needs to be further conducted. Thus, this review provides an understanding of the potential diuretic bioactive compounds of plants for further research and pharmaceutical applications.

Long-Term Visual Acuity and Optical Coherence Tomography Changes After Vitrectomy for Idiopathic Epiretinal Membranes.

Objective: To evaluate the long-term visual acuity and retinal thickness changes after pars plana vitrectomy (PPV) for idiopathic epiretinal membranes (ERM). Methods: We performed a retrospective analysis of 72 patients who underwent PPV for idiopathic ERM in a tertiary hospital over 5 consecutive years. The main outcome measurement was change in visual acuity and macular thickness as recorded with optical coherence tomography (OCT). Results: Medical records of 239 patients with a diagnosis of ERM who underwent PPV with or without internal limiting membrane (ILM) peeling were reviewed; of these, 72 patients with idiopathic ERM were included in the final analysis. All patients completed at least one year of follow-up, and 23 patients (30%) had 5 or more years of follow-up. The mean preoperative best corrected visual acuity (BCVA) was 20/65, and mean preoperative central macular thickness (CMT) on OCT was 434 microns (µm). Mean postoperative BCVA and CMT at one year were 20/40 and 303 µm, respectively (p<0.0001). A total of 42 patients (58%) improved by 2 or more lines; BCVA and CMT continued to improve postoperatively for up to 5 years of the follow-up period. There was no significant difference in BCVA or CMT between phakic and pseudophakic patients, and ILM peeling was performed in 67% of patients. Improved BCVA at 1 year was associated with younger age (p<0.0001) and ILM peeling (p=0.020). Conclusion: PPV is an effective treatment for idiopathic ERM, and ILM peel may be of benefit. BCVA continues to improve up to 2 years and beyond after surgery regardless of the duration of symptoms.

Diagnosis and management of uterine fibroids: current trends and future strategies.

Uterine fibroids (UFs), leiomyomas or myomas, are a type of malignancy that affects the smooth muscle of the uterus, and it is most commonly detected in women of reproductive age. Uterine fibroids are benign monoclonal growths that emerge from uterine smooth muscle cells (myometrium) as well as fibroblasts. Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation. It is also associated with reproductive issues like impaired fertility, conceiving complications, and adverse obstetric outcomes. It is the leading cause of gynaecological hospitalisation in the American subcontinent and a common reason for the hysterectomy. Twenty-five percent of the reproductive women experience the symptoms of uterine fibroids, and among them, around 25% require hospitalization due to the severity of the disease. The frequency of the disease remains underestimated as many women stay asymptomatic and symptoms appear gradually; therefore, the condition remains undiagnosed. The exact frequency of uterine fibroids varies depending on the diagnosis, and the population investigated; nonetheless, the incidence of uterine fibroids in reproductive women ranges from 5.4 percent to 77 percent. The uterine fibroid treatment included painkillers, supplementation with iron, vitamin D3, birth control, hormone therapy, gonadotropin-releasing hormone (GnRH) agonists, drugs modulating the estrogen receptors, and surgical removal of the fibroids. However, more research needed at the level of gene to get a keen insight and treat the disease efficiently.

Oral Disintegrating Tablets of Proton Pump Inhibitors for Chronic Gastroesophageal Reflux Disease: An Update.

Oral disintegrating tablets (ODT) offer an attractive choice for Gastroesophageal Reflux Disease (GERD) patients suffering from dysphagia. In chronic condition, GERD patient suffers from severe erosive esophagitis. Thus patients feel difficulty and pain during swallowing, which results in patient in-compliance toward medication of tablets or capsules- especially in geriatrics and pediatric patients. These symptoms of GERD patients have attracted the formulation scientists in improving the formulation methodology for such patients. Orally disintegrating tablets could increase the therapeutic impact and drug compliance in these patients. The aim of this compilation is to provide a more convenient way to develop an oral disintegrating drug delivery system of proton pump inhibitors in patients suffering from odynophagia, associated with chronic Gastroesophageal Reflux Disease (GERD). Oral disintegrating tablets (ODT), when placed on the tongue, can quickly disintegrate and release the medicament. It later dissolves or disperses in saliva without any additional water. The saliva containing drug can easily be swallowed and descends into the stomach leading to maximum absorption from the mouth, throat, and upper esophagus. The patient compliance and bio-availability of Oral disintegrating tablets (ODT) are high compared to other conventional tablets.

Synergetic Effect of Lupeol and Naringin Against Bile Duct Ligation Induced Cardiac Injury in Rats via Modulating Nitrite Level (eNos) and NF-kB /p65 Expression.

Cardiac dysfunction such as cirrhotic cardiomyopathy is more common in liver cirrhosis related disorders including primary biliary cholangitis or biliary cirrhosis and primary sclerosing cholangitis. Bile duct ligation (BDL) is an effective model of biliary cholestasis, producing oxidative damage and fibrosis. This research was designed to evaluate the effect of Lupeol and Naringin and its combination on bile duct ligation induced cardiac injury in rats. For pharmacological evaluation, rats were randomly divided into seven groups; intrahepatic cholestasis induced by ligation of the bile duct might lead to cirrhotic cardiomyopathy. The results were analyzed by physical, biochemical and histological examination. The Lupeol (100 mg/kg, p.o.), Naringin (100 mg/kg, p.o.) and its combination (100 mg/kg each) treated group significantly improved physical infarct size, biochemical (Nitrite, SOD, CAT, and GSH) and histological (heart tissue- mitochondrial function/integrity and fibrosis) alterations occurs due to BDL-ligation. This study was concluded that oral administration of Lupeol, Naringin, and its combination has a curative potential against BDL-induced cardiac injury in rats by reducing oxidative stress and inflammatory reactions, resulting in reduced heart necrosis/myocardial infarction and increased myocardial activity. It also inhibits cardiac damage in the rat heart, these effects may be linked to the NO level (eNOS) is increased and the inactivation of the NF-kB-p65 expression pathways.This study also provides new insights into the development of lupeol and Naringin combination that can be used as supportive therapy for cardiovascular diseases.

Do limbal relaxing incisions during cataract surgery still have a role?

BACKGROUND: Though Limbal Relaxing Incisions (LRI) were used widely to correct pre-existing corneal astigmatism during cataract surgery, they have been replaced recently with the more expensive methods like the use of toric Intra Ocular Lenses (IOL) and femtosecond during cataract surgery. We conducted our study to re-evaluate the role of (LRI) in correcting pre-existing moderate corneal astigmatism during cataract surgery in settings where other options are neither available nor affordable. METHODS: Retrospective analysis of all consecutive cases of LRI performed by a single surgeon at the time of cataract surgery to correct moderate corneal astigmatism (1.5-3D) in a community hospital over a period of 6 months. Corneal astigmatism, uncorrected distance visual acuity (UDVA) and best corrected distance visual acuity (CDVA) were recorded pre-operatively, 4 weeks and 3 months post-operatively. Data on age, intraocular lens (IOL) power, predictive refraction and post-operative spherical equivalent was also collected and analyzed. The number and position of LRI was determined based on the pre-existing corneal astigmatism using online calculator. RESULTS: 29 eyes of 25 patients with the mean age of 73.6 years (range: 46 to 90 years) and corneal astigmatism between 1.5 to 3D were included. Statistically significant reduction in the mean corneal astigmatism was recorded from 2.05 ± 0.45D preoperatively to 0.85 ± 0.56D postoperatively (P < 0.0001). All eyes showed reduction in astigmatism; 83% of eyes had < 1.0D post-operatively and 66% of eyes had < 0.75D. UDVA of 6/9 or better was recorded in 80% of eyes post-operatively (CDVA of 6/9 or better in 100%). The spherical equivalent was within 1.0D of the predictive refraction postoperatively in nearly all eyes (97%) and within 0.5D in 86% of the eyes. There were no peri-operative or post-operative complications were recorded in any case. CONCLUSION: Combining LRI and cataract surgery to address moderate degrees of corneal astigmatism is a safe, reliable and predictable option especially in areas where more expensive methods such as toric IOL or excimer laser are not available or affordable. LRI has no significant effect on the spherical equivalent and is an excellent tool in reducing patient's spectacle dependence.

Chrysin modulates protein kinase IKKε/TBK1, insulin sensitivity and hepatic fatty infiltration in diet-induced obese mice.

Nuclear factor kappa B cells (NF-κB) activation causes induction of the noncanonical IκB kinases (I-kappa-B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) in liver and fat after high fat diet which followed activating of cascade of counter-inflammation that conserves energy storage. Chrysin (5,7-dihydroxyflavone), a natural flavonoid, present in many plants, honey and propolis, used conventionally to treat numerous ailments. The present study was aimed to identify the protective role of chrysin on the glucose lowering and insulin sensitivity in diet induced obese (DIO) mice by regulating IKKε/TBK1. Chrysin administered therapeutically (60, 100, 200 mg/kg body weight) and preventive mode (200 mg/kg body weight) for 4 and 10 weeks respectively to DIO mice. At last fasting blood glucose, oral glucose tolerance test, serum lipid profile, as well as the expression level of IKKε/TBK1 and triglyceride in the liver tissue were assessed. DIO mice showed impaired glucose tolerance, reduced weight gain, elevated hepatic IKKε/TBK1 expression, fatty acid infiltration triglyceride and increased in plasma insulin and glucose. Chrysin in both therapeutic and preventive mode normalized the altered levels of the same. Overall chrysin improves glycemic control and insulin sensitivity through regulating expression of IKKε/TBK1 in liver of DIO mice.

Cerebroprotective effect of pterostilbene against global cerebral ischemia in rats.

AIM OF THE STUDY: The role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied. MATERIALS AND METHODS: Male SD rats (180-200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study. RESULT: The pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control. CONCLUSION: This work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.

An insight on safety, efficacy, and molecular docking study reports of N-acetylcysteine and its compound formulations.

N-acetylcysteine (NAC) is considered as the body's major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer's disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow's site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.

An Overview of Stroke: Mechanism, In vivo Experimental Models Thereof, and Neuroprotective Agents.

BACKGROUND: Stroke is one of the causes of death and disability globally. Brain attack is because of the acute presentation of stroke, which highlights the requirement for decisive action to treat it. OBJECTIVE: The mechanism and in-vivo experimental models of stroke with various neuroprotective agents are highlighted in this review. METHOD: The damaging mechanisms may proceed by rapid, nonspecific cell lysis (necrosis) or by the active form of cell death (apoptosis or necroptosis), depending upon the duration and severity and of the ischemic insult. RESULTS: Identification of injury mediators and pathways in a variety of experimental animal models of global cerebral ischemia has directed to explore the target-specific cytoprotective strategies, which are critical to clinical brain injury outcomes. CONCLUSION: The injury mechanism, available encouraging medicaments thereof, and outcomes of natural and modern medicines for ischemia have been summarized. In spite of available therapeutic agents (thrombolytics, calcium channel blockers, NMDA receptor antagonists and antioxidants), there is a need for an ideal drug for strokes.

Quality Control Standardization and Evaluation of Antimicrobial Potential of Daruhaldi (Berberis aristata DC) Stem Bark.

Berberis aristata is used for the treatment of diabetes, piles, and liver diseases. As the drug is broadly used in Indigenous systems of medicine, it was designed to set the quality standards and antimicrobial potential for the stem bark of Berberis aristata. Botanical, physicochemical, pharmacotoxicological, fluorescence, microbial load, and phytochemical parameters of the stem bark were determined. High-performance thin-layer chromatography (HPTLC) was carried out by the CAMAG-HPTLC system. Berberine, total phenolics, and flavonoids were estimated. The antimicrobial potential was determined against the bacteria Bacillus subtilis and Escherichia coli and fungi Penicillium citrinum and Aspergillus terreus. The foreign matter, foaming index, swelling index, bitterness value, resin content, loss on drying, total ash, acid-insoluble ash, water-soluble ash, heavy metals, microbial load, berberine content, total phenolic content, and total flavonoid content were found to be 0, 0, 5, 1.34, 0.86%, 2.07%, 4.33%, 0.28%, 2.66%, within limits, 6 colonies in 1/100 dilution, 0.032 mg/g, 144.04 µg/ml, and 85.61 µg/ml, respectively. Phytochemicals such as phenolics, flavonoids, and sterols were present in the methanolic extract. The fluorescences observed in UV light were of different colors in different solvents. The methanolic extract and standards exhibited antimicrobial activity at the tested concentrations against the microbial strains. Results confirmed the quality and purity of the drug B. aristata. Results also confirmed that methanolic extract of B. aristata stem bark possesses potent antimicrobial activity. Thus, the use of this quality-controlled plant-derived drug with established antimicrobial property could be of great significance in quality-control standardization and preventive and therapeutic approaches to infectious diseases.

Augmented Reversal of Cisplatin-Induced Delayed Gastric Emptying by Amla (Emblica Officinalis) Fruit Extract in Sprague-Dawley Rats.

Despite the availability of effective antiemetics, control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) is often suboptimal and there is need of an inexpensive and safer alternative. Thus, this study was designed to evaluate the effect of Emblica officinalis Gaertn (Euphorbiaceae) fruit extract (EEEO) on cisplatin-induced delayed gastric emptying in Sprague-Dawley rats so that Emblica officinalis can be clarified for its application in CINV as a potential candidate. Groups I, II, III, IV, and V rats were pretreated orally with 1% carboxymethyl cellulose (CMC, 1 mL/kg), 1% CMC (1 mL/kg), EEEO (250 mg/kg), EEEO (500 mg/kg), and ondansetron (3 mg/kg), respectively, for 5 consecutive days. Then, Group I rats received 0.1 mL of normal saline and Groups II-V rats received 10 mg/kg body weight of cisplatin intraperitoneally. Immediately after that, a test meal (1.5 mL/rat) was administered to each group, and after 30 minutes, rats were euthanized to evaluate the percentage of gastric emptying. EEEO at the specified doses reversed the cisplatin-induced delayed gastric emptying. EEEO (500 mg/kg body weight) pretreatment for 5 days before cisplatin challenge in Group IV rats significantly (p < .05) increased gastric emptying to 74.25% ± 7.19%. Reversal of cisplatin-induced delay in gastric emptying by EEEO (500 mg/kg body weight) in Group IV was significantly (p < .05) comparable to that of the ondansetron treated Group V. EEEO possesses the property to reverse the cisplatin-induced delayed gastric emptying and can be used as an antiemetic for the prevention of CINV.

Doping induced structural stability and electronic properties of GaN nanotubes.

The present paper discusses the effect of manganese doping on the structural stability and electronic band gap of chiral (2, 1), armchair (3, 3), and zigzag ((6, 0) and (10, 0)) single walled GaN nanotube by using density functional theory based Atomistix Toolkit (ATK) Virtual NanoLab (VNL). The structural stability has been analyzed in terms of minimum ground state total energy, binding, and formation energy. As an effect of Mn doping (1-4 atoms), all the GaN nanotubes taken into consideration show semiconducting to metallic transition first and after certain level of Mn doping changes its trend.