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1.
Article in English | MEDLINE | ID: mdl-39411941

ABSTRACT

AIM: To Discover novel PTP1B inhibitors by high-throughput virtual screening Background: Type 2 Diabetes is a significant global health concern. According to projections, the estimated number of individuals affected by the condition will reach 578 million by the year 2030 and is expected to further increase to 700 million deaths by 2045. Protein Tyrosine Phosphatase 1B is an enzymatic protein that has a negative regulatory effect on the pathways involved in insulin signaling. This regulatory action ultimately results in the development of insulin resistance and the subsequent elevation of glucose levels in the bloodstream. The proper functioning of insulin signaling is essential for maintaining glucose homeostasis, whereas the disruption of insulin signaling can result in the development of type 2 diabetes. Consequently, we sought to utilize PTP1B as a drug target in this investigation. OBJECTIVE: The purpose of our study was to identify novel PTP1B inhibitors as a potential treatment for managing type 2 diabetes. METHODS: To discover potent PTP1B inhibitors, we have screened the Maybridge HitDiscover database by SBVS. Top hits have been passed based on various drug-likeness rules, toxicity predictions, ADME assessment, Consensus Molecular docking, DFT, and 300 ns MD Simulations. RESULTS: Two compounds have been identified with strong binding affinity at the active site of PTP1B along with drug-like properties, efficient ADME, low toxicity, and high stability. CONCLUSION: The identified molecules could potentially manage T2DM effectively by inhibiting PTP1B, providing a promising avenue for therapeutic strategies.

2.
Curr Top Med Chem ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39253915

ABSTRACT

OBJECTIVE: In this review, we have summarized antifungal agents containing potent azole analogues. DATA ACQUISITION: The provided literature is related to the development and application of azole derivatives and has been accessed from electronic data bases such as Science direct, Google Scholar, and Pubmed using keywords such as "design, synthesis and evaluation", "azole hybrids", "diazole hybrids", "indazole derivatives", "imidazole derivatives", "triazole derivatives", "tetrazole derivatives" and related combinations. RESULT: From this review, it was identified that azole derivatives with promising antifungal activity play a vital role in drug discovery and development. The literature revealed that azole derivatives can effectively fight several types of microorganisms, such as Candida albicans, Aspergillus niger, and others. The rational design and structure‒activity relationship of these compounds are discussed in this paper, highlighting their potential as effective therapeutic options against various fungal pathogens. Moreover, this work addresses the challenges and future directions in the development of azole hybrids. The results of docking studies of several of the hybrids that the researchers provided are also summarized. CONCLUSION: The current work attempts to review such innovations, which may lead to the preparation of novel therapeutics. More research is required to confirm their safety and effectiveness in clinical practices.

3.
Curr Genomics ; 25(5): 343-357, 2024.
Article in English | MEDLINE | ID: mdl-39323624

ABSTRACT

The MALAT1, a huge non-coding RNA, recently came to light as a multifaceted regulator in the intricate landscape of breast cancer (BC) progression. This review explores the multifaceted functions and molecular interactions of MALAT1, shedding light on its profound implications for understanding BC pathogenesis and advancing therapeutic strategies. The article commences by acknowledging the global impact of BC and the pressing need for insights into its molecular underpinnings. It is stated that the core lncRNA MALAT1 has a range of roles in both healthy and diseased cell functions. The core of this review unravels MALAT1's multifaceted role in BC progression, elucidating its participation in critical processes like resistance, invasion, relocation, and proliferating cells to therapy. It explores the intricate mechanisms through which MALAT1 modulates gene expression, interacts with other molecules, and influences signalling pathways. Furthermore, the paper emphasizes MALAT1's clinical significance as a possible prognostic and diagnostic biomarker. Concluding on a forward-looking note, the review highlights the broader implications of MALAT1 in BC biology, such as its connections to therapy resistance and metastasis. It underscores the significance of deeper investigations into these intricate molecular interactions to pave the way for precision medicine approaches. This review highlights the pivotal role of MALAT1 in BC progression by deciphering its multifaceted functions beyond the genome, offering profound insights into its implications for disease understanding and the potential for targeted therapeutic interventions.

5.
Curr Pharm Des ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39051578

ABSTRACT

Skin cancer is a prevalent and sometimes lethal cancer that affects a wide range of people. UV radiation exposure is the main cause of skin cancer. Immunosuppression, environmental factors, and genetic predisposition are other contributing variables. Fair-skinned people and those with a history of sunburns or severe sun exposure are more likely to experience this condition. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are the three main forms. Melanoma poses a bigger hazard because of its tendency for metastasis, while SCC and BCC have limited metastatic potential. Genetic mutations and changes to signalling pathways such as p53 and MAPK are involved in pathogenesis. Early diagnosis is essential, and molecular testing, biopsy, dermoscopy, and visual inspection can all help. In addition to natural medicines like curcumin and green tea polyphenols, treatment options include immunotherapy, targeted therapy, radiation, surgery, and chemotherapy. Reducing the incidence of skin cancer requires preventive actions, including sun protection and early detection programs. An overview of skin cancers, including their forms, pathophysiology, diagnosis, and treatment, highlighting herbal therapy, is given in this review.

6.
Cell Biochem Biophys ; 82(2): 1309-1324, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740667

ABSTRACT

Diabetes mellitus is a serious and complex metabolic disorder characterized by hyperglycemia. In recent years natural products has gained much more interest by researchers as alternative sources for diabetes treatment. Though many potential agents are identified so far but their clinical utility is limited because of their adverse effects. Therefore, there is a keen interest in discovering natural compounds to treat diabetes efficiently with less side effects. Dalbergia latifolia is well explored because of its diverse pharmacological activities including diabetes. Therefore, the present research work aimed to identify and isolate the potential antidiabetic agents from the heart wood of Dalbergia latifolia. We successfully extracted DGN and ISG from the heartwood and evaluated their antidiabetic potential both in-vivo and in-vitro. Alpha amylase activity inhibition of ISG and DGN was found to be 99.05 ± 8.54% (IC50 = 0.6025 µg/mL) and 84.68 ± 5.2% (IC50 = 0.0216 µg/mL) respectively. Glucose uptake assay revealed DGN (158%) promoted maximum uptake than ISG (77%) over control. In vivo anti diabetic activity was evaluated by inducing diabetes in SD rats with the help of HFD and STZ (35 mg/kg body weight). After the continuous administration of DGN (5 mg/kg, 10 mg/kg) and ISG (5 mg/kg, 10 mg/kg) for 14 days, we observed the reduction in the blood glucose levels, body weight, total cholesterol, low density lipoprotein, very low-density lipoprotein, blood urea, serum creatinine, serum glutamate oxaloacetic transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase levels than vehicle group indicates the potency of ISG and DGN against diabetes.


Subject(s)
Blood Glucose , Chalcones , Dalbergia , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Rats, Sprague-Dawley , Animals , Rats , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/therapeutic use , Male , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Dalbergia/chemistry , Chalcones/pharmacology , Chalcones/chemistry , Chalcones/therapeutic use , Blood Glucose/metabolism , Wood/chemistry , alpha-Amylases/metabolism , alpha-Amylases/antagonists & inhibitors , Plant Extracts/chemistry , Plant Extracts/pharmacology
7.
J Drug Target ; 32(7): 807-819, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38749010

ABSTRACT

Short hyperglycaemic episodes trigger metabolic memory (MM) in which managing hyperglycaemia alone is not enough to tackle the progression of Diabetic nephropathy on the epigenetic axis. We used a structural similarity search approach to identify phytochemicals similar to natural epigenetic modifiers and docked with SIRT1 protein and did ADME studies. We found that UMB was 84.3% similar to esculetin. Upon docking, we found that UMB had a binding energy of -9.2 kcal/mol while the standard ligand had -11.8 kcal/mol. ADME showed UMB to be a good lead. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed it to be a good antioxidant with IC50 of 107 µg/mL and MTT stands for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) showed that it does not promote cell death. Oxidative biomarkers in vitro showed UMB was able to ameliorate glycemic memory induced by high glucose. Western blot revealed decreased histone acetylation under hyperglycaemic conditions and upon treatment with UMB along with DR, its levels increased. This led us to check our hypothesis of whether concomitant diet reversal (DR) together with UMB can alleviate high-fat diet-induced metabolic memory and diabetic nephropathy (DN) in SD rats. UMB was able to decrease blood glucose, lipid, renal, and liver profile concluding UMB was able to ameliorate DN and MM by increasing the histone acetylation level.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Epigenesis, Genetic , Animals , Diabetic Nephropathies/drug therapy , Rats , Epigenesis, Genetic/drug effects , Male , Diabetes Mellitus, Experimental/drug therapy , Antioxidants/pharmacology , Hyperglycemia/drug therapy , Sirtuin 1/metabolism , Sirtuin 1/genetics , Molecular Docking Simulation , Blood Glucose/drug effects , Blood Glucose/metabolism , Humans , Umbelliferones/pharmacology , Phytochemicals/pharmacology , Phytochemicals/administration & dosage
8.
Neurochem Int ; 177: 105760, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723900

ABSTRACT

Neurodegenerative diseases such as Parkinson's disease (PD) are characterized by the death of neurons in specific areas of the brain. One of the proteins that is involved in the pathogenesis of PD is α-synuclein (α-syn). α-Syn is a normal protein that is found in all neurons, but in PD, it misfolds and aggregates into toxic fibrils. These fibrils can then coalesce into pathological inclusions, such as Lewy bodies and Lewy neurites. The pathogenic pathway of PD is thought to involve a number of steps, including misfolding and aggregation of α-syn, mitochondrial dysfunction, protein clearance impairment, neuroinflammation and oxidative stress. A deeper insight into the structure of α-syn and its fibrils could aid in understanding the disease's etiology. The prion-like nature of α-syn is also an important area of research. Prions are misfolded proteins that can spread from cell to cell, causing other proteins to misfold as well. It is possible that α-syn may behave in a similar way, spreading from cell to cell and causing a cascade of misfolding and aggregation. Various post-translational alterations have also been observed to play a role in the pathogenesis of PD. These alterations can involve a variety of nuclear and extranuclear activities, and they can lead to the misfolding and aggregation of α-syn. A better understanding of the pathogenic pathway of PD could lead to the development of new therapies for the treatment of this disease.


Subject(s)
Parkinson Disease , Protein Folding , alpha-Synuclein , alpha-Synuclein/metabolism , Humans , Parkinson Disease/metabolism , Parkinson Disease/pathology , Animals , Lewy Bodies/metabolism , Lewy Bodies/pathology
9.
Drug Deliv Transl Res ; 14(10): 1-17, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38789909

ABSTRACT

Fisetin (FS) is a flavonoid that possesses antioxidant and anti-inflammatory properties against ulcerative colitis. FS shows poor dissolution rate and permeability. An attempt has been made to develop colon-targeted solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L) SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was prepared using Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were further converted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio of guar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200 (A-200) was added to enhance their flow characteristics. Further, they were converted into spheroids by extrusion-spheronization technique. The solid-state characterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that the crystalline form of FS was converted into the amorphous form. In the dissolution study, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug release within the first 5 h, followed by rapid release of the drug between the 5th and 10th h, indicating its release at colonic site. The site-specific delivery of FS to colon via FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies on rats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5 h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS. Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oral bioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared to unprocessed FS.


Subject(s)
Biological Availability , Colon , Emulsions , Flavonoids , Flavonols , Galactans , Pectins , Polysaccharides, Bacterial , Flavonols/pharmacokinetics , Flavonols/administration & dosage , Flavonols/chemistry , Animals , Colon/metabolism , Flavonoids/pharmacokinetics , Flavonoids/administration & dosage , Flavonoids/chemistry , Male , Administration, Oral , Galactans/chemistry , Galactans/pharmacokinetics , Galactans/administration & dosage , Pectins/chemistry , Pectins/pharmacokinetics , Pectins/administration & dosage , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/pharmacokinetics , Polysaccharides, Bacterial/administration & dosage , Plant Gums/chemistry , Plant Gums/pharmacokinetics , Plant Gums/administration & dosage , Mannans/chemistry , Mannans/pharmacokinetics , Mannans/administration & dosage , Drug Delivery Systems , Nanoparticles/chemistry , Nanoparticles/administration & dosage , Rats , Rats, Sprague-Dawley , Drug Liberation , Solubility
10.
Nat Prod Res ; : 1-6, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563125

ABSTRACT

Using structural similarity approach we identified dillapiole, a phenylpropanoid, the main component of Piper aduncum L. and Anethum graveolens L. essential oils as potential PPARγ agonist. Molecular docking revealed that dillapiole binds to the active site of PPARγ, similar to pioglitazone binding. In silico ADME studies showed that dillapiole has high water solubility and GI absorption. Dillapiole was also observed to be partial agonist of PPARγ receptors with EC50 of 43.95 µM. In BHK-21 cells cultured under hyperglycaemic conditions, dillapiole administration reduced oxidative stress and prevented decrease in histone H3 acetylation (k9/14) levels. In HFD + STZ induced diabetic mice, dillapiole treatment for 7 days was able to improve renal functions and decrease plasma glucose level to 138.39 ± 12.36 mg/dl along with decreasing total cholesterol (29%), triglycerides (48.8%), LDL (24.7%), and VLDL (65%) levels in serum. These results show that dillapiole is a potential PPARγ-agonist and thus needs to explore further.

11.
J Biochem Mol Toxicol ; 38(4): e23712, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38602238

ABSTRACT

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Kidney Diseases , Thioctic Acid , Rats , Animals , Thioctic Acid/pharmacology , Thioctic Acid/therapeutic use , Antioxidants/metabolism , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Experimental/metabolism , Rats, Wistar , Lipid Peroxidation , Catalase/metabolism , Blood Glucose/metabolism , Superoxide Dismutase/metabolism , Oxidative Stress
12.
Pharmacoepidemiol Drug Saf ; 33(4): e5791, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38565527

ABSTRACT

BACKGROUND: Self-medication practice among pregnant women is a global concern. However, its understanding in the Indian context is limited due to a lack of comprehensive studies. PURPOSE: This study aimed to comprehensively assess the prevalence of self-medication, the medications used for self-medication, diseases/conditions associated with self-medication, and the reasons for self-medication among Indian pregnant women. METHODS: This study was carried out following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A thorough search was done in PubMed, Embase, and Google Scholar to find articles that were published up until May 2023. Inclusion criteria comprised observational studies reporting self-medication prevalence among pregnant women in India. Data were extracted using a standardized sheet, and a random-effects model was applied to determine the overall prevalence of self-medication using R software. The I2 statistic was employed to assess the heterogeneity among the studies. RESULTS: This study analyzed eight studies with a collective sample size of 2208 pregnant women. The pooled prevalence of self-medication among pregnant Indian women was 19.3% (95% CI: 7.5%-41.3%; I2 = 99%; p < 0.01). Common self-treated conditions were cold, cough, fever, headache, and stomach disorders. Antipyretics, analgesics, antihistamines, and antacids were frequently used for self-medication. The perception of mild ailment, immediate alleviation, convenience, time savings, and advice from family, friends, or the media were all reasons for self-medication. Local pharmacies were the most usual source for obtaining drugs, and pharmacists, family, friends, and past prescriptions were common sources of medicine information. CONCLUSIONS: A low yet substantial number of pregnant women in India are engaged in self-medication practices. Appropriate strategies need to be planned to reduce self-medication practices to attain sustainable developmental goals for maternal health in India.


Subject(s)
Self Medication , Humans , Self Medication/statistics & numerical data , Pregnancy , Female , India , Prevalence , Pregnant Women , Pregnancy Complications/drug therapy , Pregnancy Complications/epidemiology
13.
Pathol Res Pract ; 255: 155186, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38350169

ABSTRACT

Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.


Subject(s)
MicroRNAs , Osteomyelitis , RNA, Long Noncoding , Humans , RNA, Untranslated/genetics , Osteomyelitis/genetics , Inflammation
14.
Biol Trace Elem Res ; 202(5): 1856-1865, 2024 May.
Article in English | MEDLINE | ID: mdl-37535217

ABSTRACT

Cutaneous leishmaniasis is a parasitic skin disease prevalent in many parts of the world. Zinc has been investigated for its potential role in the immune response against Leishmania parasites. This study aimed to systematically review the literature and conduct meta-analyses to evaluate the serum zinc level and efficacy of zinc therapy in cutaneous leishmaniasis. A comprehensive search of electronic databases was performed to find studies reporting serum zinc levels and the efficacy of zinc therapy in cutaneous leishmaniasis. Meta-analyses were conducted using RevMan software (version 5.4), calculating the mean difference for serum zinc levels and risk ratio for the efficacy of zinc therapy. A total of 11 studies with 1009 participants were evaluated. Five of these studies, comprising 637 participants, examined serum zinc levels; the remaining six, involving 372 individuals, examined the effectiveness of zinc therapy in treating cutaneous leishmaniasis. The results showed that the serum zinc level was significantly lower in cutaneous leishmaniasis patients compared to controls (MD: - 26.65; 95% CI: [- 42.74, - 10.57]; p = 0.001). However, zinc therapy did not demonstrate a significant clinical improvement compared to standard treatment (RR: 0.96; 95% CI: [0.74, 1.23], p = 0.73).


Subject(s)
Leishmaniasis, Cutaneous , Zinc , Humans , Zinc/therapeutic use , Leishmaniasis, Cutaneous/drug therapy
15.
Daru ; 32(1): 339-352, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38105369

ABSTRACT

OBJECTIVES: The main objective of this work was to review and summarise the detailed literature available on viral nanoparticle and the strategies utilised for their manufacture along with their applications as therapeutic agents. DATA ACQUISITION: The reported literature related to development and application of virus nanoparticles have been collected from electronic data bases like ScienceDirect, google scholar, PubMed by using key words like "viral nanoparticles", "targeted drug delivery" and "vaccines" and related combinations. RESULT: From the detailed literature survey, virus nanoparticles were identified as carriers for the targeted delivery. Due to the presence of nanostructures in virus nanoparticles, these protect the drugs from the degradation in the gastrointestinal tract and in case of the delivery of gene medicine, they carry the nucleic acids to the target/susceptible host cells. Thus, artificial viruses are utilised for targeted delivery to specific organ in biomedical and biotechnological areas. CONCLUSION: Thus, virus nanoparticles can be considered as viable option as drug/gene carrier in various healthcare sectors especially drug delivery and vaccine and can be explored further in future for the development of better drug delivery techniques.


Subject(s)
Drug Delivery Systems , Nanoparticles , Nanotechnology , Humans , Nanoparticles/chemistry , Nanotechnology/methods , Viruses/genetics , Animals , Drug Carriers/chemistry , Vaccines/administration & dosage
16.
Curr Diabetes Rev ; 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37888820

ABSTRACT

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the ß cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

17.
Curr Top Med Chem ; 23(25): 2394-2415, 2023.
Article in English | MEDLINE | ID: mdl-37828679

ABSTRACT

BACKGROUND: Piperine is a natural compound found in black pepper that has been traditionally used for various therapeutic purposes. In the ayurvedic system of medication there is a lot of evidence which shows that the piperine is widely used for different therapeutic purpose. In recent years, there has been an increasing interest in the pharmacological and therapeutic potential of piperine and its derivatives in modern medicine. In order to increase the bioavailability and therapeutic effectiveness of piperine and its analogs, researchers have been looking at various extraction methods and synthesis approaches. Many studies have been conducted in this area because of the promise of piperine as a natural substitute for synthetic medications. OBJECTIVES: The objective of this review article is to provide an up-to-date analysis of the literature on the synthesis of piperine analogs, including their extraction techniques and various biological activities such as antihypertensive, antidiabetic, insecticidal, antimicrobial, and antibiotic effects. Additionally, the review aims to discuss the potential of piperine in modern medicine, given its traditional use in various medicinal systems such as Ayurveda, Siddha, and Unani. The article also provides a comprehensive analysis of the plant from which piperine is derived. CONCLUSION: This review article provides a thorough examination of piperine and the source plant. The best extraction technique for the extraction of piperine and the synthesis of its analogs with various biological activities, including antihypertensive, antidiabetic, insecticidal, antibacterial, and antibiotic properties, are covered in the article. This review aims to provide an updated analysis of the literature on the synthesis of piperine analogs.


Subject(s)
Alkaloids , Antihypertensive Agents , Alkaloids/pharmacology , Polyunsaturated Alkamides/pharmacology , Benzodioxoles/pharmacology , Hypoglycemic Agents , Anti-Bacterial Agents
19.
Eur J Pharmacol ; 954: 175832, 2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37329974

ABSTRACT

The onset and progression of Alzheimer's disease (AD) are influenced by a variety of factors. These include oxidative stress, overexpression of acetylcholinesterase (AChE), depletion of acetylcholine levels, increased beta-secretase mediated conversion of Amyloid Precursor Protein (APP) to Amyloid Beta (Abeta), accumulation of Abeta oligomers, decrease in Brain Derived Neurotrophic factor (BDNF) and accelerated neuronal apoptosis due to elevated levels of caspase-3. The currently available therapeutic approaches are inadequate in affecting these pathological processes except maybe the overexpression of AChE (AChE inhibitors like donepezil, rivastigmine). There is an urgent need to develop disease modifying pharmacotherapeutic interventions which have appreciable safety and cost effectiveness. From previously reported in vitro studies and a preliminary assessment of neuroprotective effect in scopolamine induced dementia-like cognitive impairment in mice, vanillin has been used as the compound of interest in the present study. Vanillin, a phytoconstituent, has been used in humans, safely, in the form of a flavouring agent for various foods, beverages, and cosmetics. Owing to its chemical nature i.e. being a phenolic aldehyde, it has an additional antioxidant property that is congruent to the desirable characteristics that are sought in a suitable novel anti-AD agent. In our study, vanillin proved to have a nootropic effect in healthy Swiss albino mice as well as an ameliorative effect in aluminium chloride and D-galactose induced AD model in mice. Apart from tackling oxidative stress, vanillin was found to reduce the levels of AChE, beta secretase, caspase-3, enhance degradation of Abeta plaques and elevate the levels of BDNF, in cortical and hippocampal regions. Vanillin is a promising candidate for being incorporated into the search for safe and effective anti-AD molecules. However, further research might be needed to warrant its application clinically.


Subject(s)
Alzheimer Disease , Humans , Mice , Animals , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Aluminum Chloride , Amyloid beta-Peptides/metabolism , Galactose/adverse effects , Caspase 3/metabolism , Brain-Derived Neurotrophic Factor , Acetylcholinesterase/metabolism , Disease Models, Animal
20.
Pharmaceutics ; 15(2)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36839773

ABSTRACT

Coronavirus, a causative agent of the common cold to a much more complicated disease such as "severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)", is a member of the coronaviridae family and contains a positive-sense single-stranded RNA of 26-32 kilobase pairs. COVID-19 has shown very high mortality and morbidity and imparted a significantly impacted socioeconomic status. There are many variants of SARS-CoV-2 that have originated from the mutation of the genetic material of the original coronavirus. This has raised the demand for efficient treatment/therapy to manage newly emerged SARS-CoV-2 infections successfully. However, different types of vaccines have been developed and administered to patients but need more attention because COVID-19 is not under complete control. In this article, currently developed nanotechnology-based vaccines are explored, such as inactivated virus vaccines, mRNA-based vaccines, DNA-based vaccines, S-protein-based vaccines, virus-vectored vaccines, etc. One of the important aspects of vaccines is their administration inside the host body wherein nanotechnology can play a very crucial role. Currently, more than 26 nanotechnology-based COVID-19 vaccine candidates are in various phases of clinical trials. Nanotechnology is one of the growing fields in drug discovery and drug delivery that can also be used for the tackling of coronavirus. Nanotechnology can be used in various ways to design and develop tools and strategies for detection, diagnosis, and therapeutic and vaccine development to protect against COVID-19. The design of instruments for speedy, precise, and sensitive diagnosis, the fabrication of potent sanitizers, the delivery of extracellular antigenic components or mRNA-based vaccines into human tissues, and the administration of antiretroviral medicines into the organism are nanotechnology-based strategies for COVID-19 management. Herein, we discuss the application of nanotechnology in COVID-19 vaccine development and the challenges and opportunities in this approach.

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