Publications by authors named "Ankit Awasthi"

31 Publications

Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.

Med Hypotheses 2021 Sep 15;154:110644. Epub 2021 Jul 15.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.

Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.
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http://dx.doi.org/10.1016/j.mehy.2021.110644DOI Listing
September 2021

Recent updates on animal models for understanding the etiopathogenesis of polycystic ovarian syndrome.

Life Sci 2021 Sep 23;280:119753. Epub 2021 Jun 23.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Australia.

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.
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http://dx.doi.org/10.1016/j.lfs.2021.119753DOI Listing
September 2021

Sweet pepper and its principle constituent capsiate: functional properties and health benefits.

Crit Rev Food Sci Nutr 2021 May 6:1-25. Epub 2021 May 6.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

Capsiate is a non-pungent analogue of capsaicin. It belongs to the family of capsinoids which are esters of vanillyl alcohol with fatty acids while capsaicin belongs to the family of capsaicinoids that are amides of vanillylamine with a variety of branched-chain fatty acids. While capsaicin is extensively reported for plethora of pharmacological actions, capsiate remains much less explored. Extracted from various species of Capsicum plant, the molecule has also been chemically synthesized via a number of synthetic and enzymatic routes. Based on its action on transient receptor potential vanilloid subfamily member 1 receptors, recent research has focused on its potential roles in treatment of obesity, metabolic disorders, cancer, cardiovascular disorders and gastro-intestinal disorders. Its toxicity profile has been reported to be much safe. The molecule, however, faces the challenge of low aqueous solubility and stability. It has been commercialized for its use as a weight loss supplement. However, the therapeutic potential of the compound which is much beyond boosting metabolism remains unexplored hitherto. This comprehensive review summarizes the studies demonstrating the therapeutic potential of capsiate in various pathological conditions. Discussed also are potential future directions for formulation strategies to develop efficient, safe and cost-effective dosage forms of capsiate to explore its role in various disease conditions. The databases investigated include Cochrane library, Medline, Embase, Pubmed and in-house databases. The search terms were "capsiate," "capsinoids," "thermogenesis," and their combinations. The articles were screened for relevance by going through their abstract. All the articles pertaining to physicochemical, physiological, pharmacological and therapeutic effects of capsiate have been included in the manuscript.
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http://dx.doi.org/10.1080/10408398.2021.1913989DOI Listing
May 2021

Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications.

Expert Opin Drug Deliv 2021 04 27;18(4):427-448. Epub 2020 Dec 27.

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.

: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
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http://dx.doi.org/10.1080/17425247.2021.1846517DOI Listing
April 2021

Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations.

Curr Neuropharmacol 2021 ;19(7):957-989

Department of Biotechnology, School of Bioengineering and Biosciences, Faculty of Technology and Sciences, Lovely Professional University, Phagwara-144411, Punjab, India.

Huntington's disease (HD) is an autosomal fatal genetic disease in which degeneration of neuronal cells occurs in the central nervous system (CNS). Commonly used therapeutics are cludemonoamine depletors, antipsychotics, antidepressants, and tranquilizers. However, these drugs cannot prevent the psychotic, cognitive, and behavioral dysfunctions associated with HD. In addition to this, their chronic use is limited by their long-term side effects. Herbal drugs offer a plausible alternative to this and have shown substantial therapeutic effects against HD. Moreover, their safety profile is better in terms of side effects. However, due to limited drug solubility and permeability to reach the target site, herbal drugs have not been able to reach the stage of clinical exploration. In recent years, the paradigm of research has been shifted towards the development of herbal drugs based nanoformulations that can enhance their bioavailability and blood-brain barrier permeability. The present review covers the pathophysiology of HD, available biomarkers, phytomedicines explored against HD, ongoing clinical trials on herbal drugs exclusively for treating HD and their nanocarriers, along with their potential neuroprotective effects.
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http://dx.doi.org/10.2174/1570159X18666201109090824DOI Listing
January 2021

Treatment Strategies Against Diabetic Foot Ulcer: Success so Far and the Road Ahead.

Curr Diabetes Rev 2021 ;17(4):421-436

School of Pharmaceutical Sciences, Lovely Professional University Phagwara, 144411, Punjab, India.

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It is associated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. There are four stages of wound healing, namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In the case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Conventional dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer for many years.

Introduction: In this review, the global prevalence as well as etiopathogenesis related to diabetic foot ulcer have been discussed. The potential role of various synthetic and herbal drugs, as well as their conventional dosage forms in the effective management of DFU have been discussed in detail.

Methods: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU.

Results: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action.

Conclusion: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU.
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http://dx.doi.org/10.2174/1573399816999201102125537DOI Listing
May 2021

Recent advances in intraocular and novel drug delivery systems for the treatment of diabetic retinopathy.

Expert Opin Drug Deliv 2021 05 14;18(5):553-576. Epub 2020 Dec 14.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.

: Diabetic retinopathy (DR) is associated with damage to the retinal blood vessels that lead eventually to vision loss. The existing treatments of DR are invasive, expensive, and cumbersome. To overcome challenges associated with existing therapies, various intraocular sustained release and novel drug delivery systems (NDDS) have been explored.: The review discusses recently developed intraocular devices for sustained release of drugs as well as novel noninvasive drug delivery systems that have met a varying degree of success in local delivery of drugs to retinal circulation.: The intraocular devices have got very good success in providing sustained release of drugs in patients. The development of NDDS and their application through the ocular route has certainly provided an edge to treat DR over existing therapies such as anti-VEGF administration but their success rate is quite low. Moreover, most of them have proved to be effective only in animal models. In addition, the extent of targeting the drug to the retina still remains variable and unpredictable. The toxicity aspect of the NDDS has generally been neglected. In order to have successful commercialization of nanotechnology-based innovations well-designed clinical research studies need to be conducted to evaluate their clinical superiority over that of the existing formulations.
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http://dx.doi.org/10.1080/17425247.2021.1846518DOI Listing
May 2021

Nanocarriers for treatment of dermatological diseases: Principle, perspective and practices.

Eur J Pharmacol 2021 Jan 28;890:173691. Epub 2020 Oct 28.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India.

Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.
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http://dx.doi.org/10.1016/j.ejphar.2020.173691DOI Listing
January 2021

Depression and anxiety in patients of chronic kidney disease undergoing haemodialysis: A study from western Rajasthan.

J Family Med Prim Care 2020 Aug 25;9(8):4282-4286. Epub 2020 Aug 25.

Department of Psychiatry, Dr. S. N. Medical College, Jodhpur, Rajasthan, India.

Background And Aims: Chronic kidney disease (CKD) is a long standing debilitating medical condition. CKD patients who are undergoing hemodialysis commonly experience depressive and anxiety symptoms because of various physical and psychosocial factors. The present study aimed to assess psychiatric morbidities i.e., depression and/or anxiety in patients with CKD undergoing hemodialysis. The objective of study was to evaluate depressive and anxiety disorders and their relation to socio-demographic factors in patients with CKD.

Materials And Methods: A cross-sectional study was conducted at Nephrology department of a tertiary care institution on 100 CKD patients undergoing hemodialysis; who fulfilled the inclusion criteria. Diagnosis of depression and anxiety disorder was made as per WHO (ICD-10) criteria. Hospital Anxiety and Depression scale (HADS) was applied to study severity of the disorders. Data collected was subjected to suitable statistical analysis (mean, standard deviation and Chi-square test).

Results: Majority (54 percent) of the CKD patients belonged to age group of 41 to 60 years, were Hindus, married and had low monthly income. The prevalence of depressive disorder and anxiety disorder among CKD patients was around 66% and 61%, respectively. Depression and anxiety were significantly associated with gender, occupation, income and duration of haemodialysis in these patients.

Conclusion: Depression and anxiety are highly prevalent in CKD patients and have varying relations with different socio-demographic characteristics of patients. Clinicians should focus on these morbidities while managing such patients and provide holistic treatment using multidisciplinary approaches to improve the overall quality of life.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_840_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586630PMC
August 2020

Exploring role of probiotics and Ganoderma lucidum extract powder as solid carriers to solidify liquid self-nanoemulsifying delivery systems loaded with curcumin.

Carbohydr Polym 2020 Dec 29;250:116996. Epub 2020 Aug 29.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India.

Solid self-nanoemulsifying drug delivery system (S-SENDDS) containing Curcumin (CRM) were prepared using combination of Ganoderma lucidum extract powder (GLEP) and probiotics (PB) as carriers. Liquid SNEDDS containing CRM were prepared by mixing Capmul MCM, Labrafil M1944CS, Tween 80 and Transcutol P. These were further spray dried and finally converted into spheroids. The droplet size of reconstituted S-SNEDDS powder and spheroids was found in the range of 35 to 37 nm, zeta potential in the range of - 21.48 to -23.22 mV and drug loading in the range of 95-96%. The release of drug from formulations was found to be more than 90%. Similarly, significant improvement (p < 0.05) in permeability of CRM was observed through SNEDDS using Caco2 cell lines. The non-significant difference (p> 0.05) in drug loading, droplet size, dissolution rate and angle of repose between L-SNEDDS and S-SNEDDS indicated the potential of GLEP-PB to produce stable SNEDDS.
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http://dx.doi.org/10.1016/j.carbpol.2020.116996DOI Listing
December 2020

Fecal Microbiota Transplant: Latest Addition to Arsenal Against Recurrent Clostridium Difficile Infection.

Recent Pat Antiinfect Drug Discov 2020 Sep 24. Epub 2020 Sep 24.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab- 144411. India.

An infectious disease of colon, recurrent Clostridium difficile infection (RCDI) is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics is considered to be responsible for the etiopathogenesis of rCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti-infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control recurrence of disease, Fecal Microbiota Transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections (RCDI). In last three decades a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, very small number of patents could be found in the area indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.
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http://dx.doi.org/10.2174/1574891X15666200925092354DOI Listing
September 2020

Flavonoids as Potential Therapeutic Agents for the Management of Diabetic Neuropathy.

Curr Pharm Des 2020 ;26(42):5468-5487

Department of Pharmacy, Tishk International University-Erbil, Kurdistan Region, Iraq.

Flavonoids are secondary metabolites that are widely distributed in plants. These phenolic compounds are classified into various subgroups based on their structures: flavones, flavonols, isoflavones, flavanones, and anthocyanins. They are known to perform various pharmacological actions like antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic and antiallergic, etc. Diabetes is a chronic progressive metabolic disorder that affects several biochemical pathways and leads to secondary complications such as neuropathy, retinopathy, nephropathy, and cardiomyopathy. Among them, the management of diabetic neuropathy is one of the major challenges for physicians as well as the pharmaceutical industries. Naturally occurring flavonoids are extensively used for the treatment of diabetes and its related complications due to their antioxidant properties. Moreover, flavonoids inhibit various pathways that are involved in the progression of diabetic neuropathy like the reduction of oxidative stress, decrease in glycogenolysis, increase glucose utilization, decrease in the formation of advanced glycation end products, and inhibition of the α-glucosidase enzyme. This review entails current updates on the therapeutic perspectives of flavonoids in the treatment of neuropathic pain. This manuscript explains the pathological aspects of neuropathic pain, the chemistry of flavonoids, and their application in amelioration of neuropathic pain through preclinical studies either alone or in combination with other therapeutic agents.
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http://dx.doi.org/10.2174/1381612826666200826164322DOI Listing
April 2021

OUTBREAK of novel corona virus disease (COVID-19): Antecedence and aftermath.

Eur J Pharmacol 2020 Oct 25;884:173381. Epub 2020 Jul 25.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.

Outbreak of Coronavirus disease 2019 (COVID-19) started in mid of December 2019 and spread very rapidly across the globe within a month of its outbreak. Researchers all across the globe started working to find out its possible treatments. However, most of initiatives taken were based on various hypotheses and till date no successful treatments have been achieved. Some strategies adopted by China where existing antiviral therapy was initially used to treat COVID-19 have not given very successful results. Researchers from Thailand explored the use of combination of anti-influenza drugs such as Oseltamivir, Lopinavir and Ritonavir to treat it. In some cases, combination therapy of antiviral drugs with chloroquine showed better action against COVID-19. Some of the clinical studies showed very good effect of chloroquine and hydroxychloroquine against COVID-19, however, they were not recommended due to serious clinical toxicity. In some cases, use of rho kinase inhibitor, fasudil was found very effective. In some of the countries, antibody-based therapies have proved fairly successful. The use of BCG vaccines came in light; however, they were not found successful due to lack of full-proof mechanistic studies. In Israel as well as in other developed countries, pluristems allogeneic placental expanded cell therapy has been found successful. Some phytochemicals and nutraceuticals have also been explored to treat it. In a recent report, the use of dexamethasone was found very effective in patients suffering from COVID-19. Its effect was most striking among patients on ventilator. The research for vaccines that can prevent the disease is still going on. In light of the dynamic trends, present review focuses on etiopathogenesis, factors associated with spreading of the virus, and possible strategies to treat this deadly infection. In addition, it attempts to compile the recent updates on development of drugs and vaccines for the dreaded disease.
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http://dx.doi.org/10.1016/j.ejphar.2020.173381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381902PMC
October 2020

Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against rotenone-induced Parkinson's disease rat model.

Food Chem Toxicol 2020 Oct 23;144:111590. Epub 2020 Jul 23.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.

Fisetin (FS) was reported to have various pharmacological activities. But due to its lower aqueous solubility and oral bioavailability, it is not in much use. As solubility and bioavailability plays and important role in the pharmacological activity, in this research work we tried to improve the oral bioavailability of fisetin. In this research work, we developed self-nanoemulsifying drug delivery system (SNEDDS) of fisetin. Developed SNEDDS were subjected for pharmacokinetic and pharmacodynamics studies against rotenone-induced Parkinson's disease (PD) model in rats. Higher Cmax and area under the curve during pharmacokinetic study indicated that SNEDDS improved the oral bioavailability of FS and also increased the mean residence time of drug in plasma. Results of behavior parameters (locomotor, muscle co-ordination and catalepsy), biochemical estimation (TBARS, nitrite, GSH, SOD and CAT) and ELISA (soluble alfa synuclein, BDNF, TNF-α and IL-6) confirmed the significantly improved (p < 0.05) neuroprotection in rats treated with FS loaded SNEDDS as compared to rats treated with naïve FS. This study suggests that SNEDDS improved the oral bioavailability of FS which further helped in improving its neuroprotective activity in rat model of PD. It further suggests the potential use of FS-SNEDDS in effective management of PD condition.
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http://dx.doi.org/10.1016/j.fct.2020.111590DOI Listing
October 2020

Therapeutic potential of mushrooms in diabetes mellitus: Role of polysaccharides.

Int J Biol Macromol 2020 Dec 18;164:1194-1205. Epub 2020 Jul 18.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.

Diabetes mellitus is a metabolic disorder due to increased level of glucose in blood that affects millions of individuals. If not managed properly, it can lead to life threatening complications, organ failure and mortality. Research has recognized that diabetes can be prevented and managed by following proper lifestyle which includes diet and exercise. Though a number of synthetic drugs are available for managing this condition, their long-term use is associated with many side effects. This has shifted the research towards medicinal plants and herbs which are considered to be comparatively safe. Edible mushrooms belong to the class of potential anti-diabetic phytotherapy. They are rich in natural compounds such as fibers, polysaccharides, phenolics and alkaloids and known for providing antidiabetic, antioxidant and antihyperlipidemic effects from ancient times. Moreover, mushroom polysaccharides also act as prebiotics and modulate the composition of gut microflora; and thus, can reduce insulin resistance. The present review discusses the pathophysiology of diabetes and, elaborates some potential mushroom species that are known to have antihyperglycemic activities. Different mushroom polysaccharides modulating the composition of gut microflora in diabetic animal models have also been discussed.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.145DOI Listing
December 2020

Validated Reverse Phase-High-Performance Liquid Chromatography Method for Estimation of Fisetin in Self-Nanoemulsifying Drug Delivery System.

Assay Drug Dev Technol 2020 Aug/Sep;18(6):274-281. Epub 2020 Jun 29.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

Fisetin (FS) is a polyphenolic phytoconstituent reported to have various pharmacological activities such as antioxidant, antiparkinsonian, and antidepressant. An analytical method was developed and validated for the estimation of FS by ultrafast liquid chromatography using C-18 reverse phase column. Acetonitrile and orthophosphoric acid (0.2% v/v) in the ratio of 30:70 v/v was used as mobile phase. Flow rate was set at 1 mL/min. Chromatogram of FS was detected at wavelength of 362 nm. Retention time for FS was found to be 7.06 min. The developed method was found to be linear in the range of 2-10 μg/mL with regression coefficient of 0.9985. The method was validated as per the International Conference on Harmonization (ICH) Q2 (R1) guidelines. The percentage recovery was in the range of 95%-105%, which indicated the accuracy of the method. The percentage relative standard deviation (RSD) was found to be <2%, which indicates the precision of the method. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.46 and 1.41 μg/mL, respectively. The developed method was found to be robust as there was no significant change in response with change in flow rate, ratio of mobile phase, and pH. The method was successfully applied for estimation of drug loading and drug release from self-nanoemulsifying drug delivery system (SNEDDS). The % drug loading of FS in prepared liquid SNEDDS formulation was found to be 101.95%. The results of dissolution studies indicated 67.78% FS release in water at the end of 60 min.
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http://dx.doi.org/10.1089/adt.2020.983DOI Listing
September 2021

Multiple target-based combination therapy of galantamine, memantine and lycopene for the possible treatment of Alzheimer's disease.

Med Hypotheses 2020 Oct 25;143:109879. Epub 2020 May 25.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.

Alzheimer's disease is type of dementia in which cognitive functions get declined. More than 50 million people are affected by this disease across the world. Many clinical and preclinical studies have been conducted on the treatment of AD but very limited number of drugs have found a clinical application. Because regeneration of neuron is a complicated process due to the involvement of multiple pathways, a combination of drugs that can work through multiple pathways could prove to be effective in treating AD. Based on prior studies and different mechanisms involved in the treatment, a new hypothesis has been proposed that a combination of galantamine, memantine and lycopene is anticipated to produce better activity as compared to the current therapies available in market for the treatment of this disease.
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http://dx.doi.org/10.1016/j.mehy.2020.109879DOI Listing
October 2020

Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid.

Drug Dev Ind Pharm 2020 Apr 23;46(4):597-605. Epub 2020 Mar 23.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, -19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be  57.32 ± 1.87 nm,  0.261 ± 0.043, -16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (<.05) improvement in dissolution rate of drug in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) as compared to unprocessed DHA. In both the dissolution media, the dissolution rate was found more that 85% in 90 min. Absence of drug precipitation, phase separation, and turbidity during thermodynamic stability studies indicated that the developed SNEDDS were stable. Hence, it was concluded that SNEDDS have offered sufficient stability as well as dissolution rate of DHA.
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http://dx.doi.org/10.1080/03639045.2020.1742143DOI Listing
April 2020

Modified apple polysaccharide capped gold nanoparticles for oral delivery of insulin.

Int J Biol Macromol 2020 Apr 1;149:976-988. Epub 2020 Feb 1.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.

The study entailed formulation of gold nanoparticles (AuNPs) upon reduction of chloroauric acid by modified apple polysaccharide (MAP). AuNPs were conjugated with insulin (INS) for its oral delivery to treat type 1 diabetes mellitus (DM). The size of MAP conjugated AuNPs loaded with INS was 124 ± 8.55 nm with zeta potential -10.5 ± 0.54 mV. The animal study carried out in streptozotocin induced rat model revealed that AuNPs conjugated insulin (AuNPs-INS) in high dose caused 3.36 folds decrease in blood glucose level in 240 min, whereas, orally administered INS failed to decrease the blood glucose level. The 28-day study also revealed better improvement in body weight, lipid profile, urea, creatinine and liver parameters in AuNPs-INS (high dose) for which the observed value was close with respect to intraperitoneally administrated insulin followed by medium dose of AuNPs-INS, low dose of AuNPS-INS, AuNPs alone and modified apple polysaccharide.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.302DOI Listing
April 2020

Treatment Strategies Against Psoriasis: Principle, Perspectives and Practices.

Curr Drug Deliv 2020 ;17(1):52-73

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara - 144411, Punjab, India.

Background: Psoriasis is a genetically predisposed autoimmune disease mediated by cytokines released by the activated immune cells. It manifests inflammatory, scaly red or white silvery flaky skin which may be a fluid-filled lesion with soreness and itchiness. The prevalence rate of psoriasis is increasing day by day. Despite having such a high prevalence rate, the treatment of psoriasis is still limited. Hence, there is a need to rethink the various treatment strategies available in the allopathic as well as in the alternative systems of medicine.

Methods: Various bibliographic databases of previously published peer-reviewed research papers were explored and systematic data culminated in terms of various treatment strategies used for the management of psoriasis. The prime focus is given towards modern as well as alternative systems of medicine such as phototherapy, a combination of phototherapy with pharmacotherapy such as Ayurveda, Yoga and naturopathy, Unani, Siddha, and Homeopathy to treat psoriasis.

Results: A comprehensive review of 161 papers, including both research and review articles, was carried out to make the article readily understandable. The pathogenesis including inflammatory mediators and type of psoriasis is discussed before the treatment strategies to understand the pathophysiology of the disease. The uniqueness, procedure, advantages, and limitations of conventional, advanced, and traditional systems of medicine to treat psoriasis are discussed in detail. Emphasis has also been given towards marine sources such as fish oil, marine sponges, and algae.

Conclusion: Although there are many modern and alternative treatment strategies available to treat psoriasis, none of them have been proven to provide complete relief to patients. Moreover, they are associated with certain side effects. In order to overcome them, novel drug delivery systems have been utilized and found effective; however, their stability and safety become the major impediments towards their successful positioning. Traditional and alternative treatment strategies have found to be safe and effective but their use is localized to certain areas. In a nutshell, to achieve successful treatment of psoriasis, there is a need to focus on the development of stable and non-toxic novel drug delivery systems or the promotion of traditional systems to treat psoriasis.
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http://dx.doi.org/10.2174/1567201816666191120120551DOI Listing
December 2020

Enhancing the potential preclinical and clinical benefits of quercetin through novel drug delivery systems.

Drug Discov Today 2020 01 7;25(1):209-222. Epub 2019 Nov 7.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.

Quercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the development of various diseases. Despite its proven therapeutic potential, the clinical use of quercetin remains limited because of its low aqueous solubility, bioavailability, and substantial first-pass metabolism. To overcome this, several novel formulations have been reported. In this review, we focus on the applications of quercetin extract as well as its novel formulations for treating different disorders. We also examine its proposed mechanism of action of quercetin.
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http://dx.doi.org/10.1016/j.drudis.2019.11.001DOI Listing
January 2020

Gold nanoparticles: New routes across old boundaries.

Adv Colloid Interface Sci 2019 Dec 17;274:102037. Epub 2019 Oct 17.

Department of Pharmacognosy, Faculty of Pharmacy, Ishik University, Erbil, Kurdistan, Iraq.

In recent years, gold nanoparticles have emerged as unique non-invasive drug carriers for targeting drugs to their site of action. Their site specificity has helped in increasing drugs' efficacy at lower dose as well as reduction in their side effects. Moreover, their excellent optical properties and small size offer their utilization as diagnostic tools to diagnose tumors as well as other diseases. This review focuses on various approaches that have been used in last several years for preparation of gold nanoparticles, their characterization techniques and theranostic applications. Their toxicity related aspects are also highlighted. Gold nanoparticles are useful as theranostic agents, owing to their small size, biocompatible nature, size dependent physical, chemical and optical properties etc. However, the challenges associated with these nanoparticles such as scale up, cost, low drug payload, toxicity and stability have been the major impediments in their commercialization. The review looks into all these critical issues and identifies the possibilities to overcome these challenges for successful positioning of metallic nanoparticles in market.
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http://dx.doi.org/10.1016/j.cis.2019.102037DOI Listing
December 2019

Treatment strategies against diabetes: Success so far and challenges ahead.

Eur J Pharmacol 2019 Nov 23;862:172625. Epub 2019 Aug 23.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Australia.

The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail.
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http://dx.doi.org/10.1016/j.ejphar.2019.172625DOI Listing
November 2019

A Systematic Review on Synthetic Drugs and Phytopharmaceuticals Used to Manage Diabetes.

Curr Diabetes Rev 2020 ;16(4):340-356

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara - 144411, Punjab, India.

Background: Diabetes is a multifactorial disease and a major cause for many microvascular and macrovascular complications. The disease will ultimately lead to high rate mortality if it is not managed properly. Treatment of diabetes without any side effects has always remained a major challenge for health care practitioners.

Introduction: The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed.

Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was sorted in terms of various approaches that are used for the treatment of diabetes.

Results: More than 170 papers including both research and review articles, were included in this review in order to produce a comprehensive and easily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in the management of diabetes is also highlighted.

Conclusion: Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination, can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics are a more holistic therapy due to their natural origin and traditional use.
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http://dx.doi.org/10.2174/1573399815666190822165141DOI Listing
June 2020

Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.

Science 2019 01 13;363(6422). Epub 2018 Dec 13.

Trans-synaptic Signaling Group, European Neuroscience Institute, 37077 Goettingen, Germany.

Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.
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http://dx.doi.org/10.1126/science.aav1483DOI Listing
January 2019

A journey from custodial to community-based care: Psychiatric Centre, Jodhpur.

Indian J Psychiatry 2018 Feb;60(Suppl 2):S224-S226

Department of Psychiatry, Dr. S. N. Medical College/Psychiatric Centre, Jodhpur, Rajasthan, India.

Since 1979, consistent and untiring efforts of Dr. D.R. Purohit, Dr. Mahaveer Chand Jain and Dr. G. D. Koolwal against the odds have brought remarkable changes in the Psychiatric centre, Jodhpur.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_446_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836342PMC
February 2018

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus.

Nat Commun 2017 07 19;8:15878. Epub 2017 Jul 19.

Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, Goettingen 37077, Germany.

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine-via α2β2-containing nicotinic receptors-to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.
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http://dx.doi.org/10.1038/ncomms15878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524938PMC
July 2017

Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.

Cereb Cortex 2018 04;28(4):1087-1104

Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany.

Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) - a molecule essential for long-term potentiation of synaptic strength - upregulated and recruited copine-6 to dendritic spines in hippocampal neurons. Overexpression of copine-6 increased mushroom spine number and decreased filopodia number, while copine-6 knockdown had the opposite effect and dramatically increased the number of filopodia, which lacked PSD95. Functionally, manipulation of post-synaptic copine-6 levels affected miniature excitatory post-synaptic current (mEPSC) kinetics and evoked synaptic vesicle recycling in contacting boutons, and post-synaptic knockdown of copine-6 reduced hippocampal LTP and increased LTD. Mechanistically, copine-6 promotes BDNF-TrkB signaling and recycling of activated TrkB receptors back to the plasma membrane surface, and is necessary for BDNF-induced increases in mushroom spines in hippocampal neurons. Thus copine-6 regulates BDNF-dependent changes in dendritic spine morphology to promote synaptic plasticity.
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http://dx.doi.org/10.1093/cercor/bhx009DOI Listing
April 2018

A novel method for culturing stellate astrocytes reveals spatially distinct Ca2+ signaling and vesicle recycling in astrocytic processes.

J Gen Physiol 2017 Jan 1;149(1):149-170. Epub 2016 Dec 1.

Trans-Synaptic Signaling Group, European Neuroscience Institute Göttingen, 37077 Göttingen, Germany

Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca fluctuations: In astrocytes transduced with GFAP promoter-driven Lck-GCaMP3, spontaneous Ca events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7 astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca signaling and vesicle recycling and dynamics in astrocytic processes.
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http://dx.doi.org/10.1085/jgp.201611607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217085PMC
January 2017

HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models.

J Clin Invest 2015 Sep 17;125(9):3572-84. Epub 2015 Aug 17.

Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies for these diseases are lacking. Here, we evaluated mouse models of age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity in the brain and peripheral organs. We determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression. In both amyloid and aging models, inflammation was associated with increased gene expression linked to a subset of transcription factors, while plasticity gene deregulation was differentially mediated. Amyloid pathology impaired histone acetylation and decreased expression of plasticity genes, while aging altered H4K12 acetylation-linked differential splicing at the intron-exon junction in neurons, but not nonneuronal cells. Furthermore, oral administration of the clinically approved histone deacetylase inhibitor vorinostat not only restored spatial memory, but also exerted antiinflammatory action and reinstated epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This study provides a systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and suggests that histone deacetylase inhibitors should be further explored as a cost-effective therapeutic strategy against age-associated cognitive decline.
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http://dx.doi.org/10.1172/JCI79942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588238PMC
September 2015
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