Mandeep Kumar Arora
@dituniversity.edu.in
Associate Professor and Head
DIT University Dehradun
EDUCATION
M.Pharm (Pharmacology), Ph.D
RESEARCH INTERESTS
Vascular Phamacology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Lakhveer Singh, Mandeep Kumar Arora, Priyanshu Kumar, Saumaya Rustogi, Shashank Shekher Mishra, and Manoj Gadewar
CRC Press
Atul Khurana, Mandeep Kumar Arora, and Harikesh Dubey
Springer Science and Business Media LLC
Sabya Sachi Das, Devanshi Sharma, Balaga Venkata Krishna Rao, Mandeep Kumar Arora, Janne Ruokolainen, Mukesh Dhanka, Hemant Singh, and Kavindra Kumar Kesari
Royal Society of Chemistry (RSC)
Injectable hydrogels have the potential to revolutionize therapeutics.
Saumya Rastogi, Shashank Shekher Mishra, Mandeep Kumar Arora, Gaurav Kaithwas, Sugato Banerjee, Velayutham Ravichandiran, Subhadeep Roy, and Lakhveer Singh
Elsevier BV
Uddipak Rai, Dhirodatta Senapati, and Mandeep Kumar Arora
Springer Science and Business Media LLC
Mohd. Imran, Mohammed Kanan Alshammari, Mandeep Kumar Arora, Amit Kumar Dubey, Sabya Sachi Das, Mehnaz Kamal, Abdulaziz Saad Abdulrahman Alqahtani, Mohammed Ahmed Yahya Sahloly, Ahmed Hammad Alshammari, Hessah Mohammed Alhomam,et al.
MDPI AG
The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.
Lakhveer Singh, Lakshmi Nair, Dinesh Kumar, Mandeep Kumar Arora, Sakshi Bajaj, Manoj Gadewar, Shashank Shekher Mishra, Santosh Kumar Rath, Amit Kumar Dubey, Gaurav Kaithwas,et al.
Frontiers Media SA
It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.
Kumud Joshi, Madhubanti Das, Anupam Sarma, Mandeep K. Arora, Manmohan SInghal, and Bhavna Kumar
Bentham Science Publishers Ltd.
Abstract: Cardiac circadian rhythms are an important regulator of body functions, including car-diac activities and blood pressure. Disturbance of circadian rhythm is known to trigger and aggra-vate various cardiovascular diseases. Thus, modulating the circadian rhythm can be used as a ther-apeutic approach to cardiovascular diseases. Through this work, we intend to discuss the current understanding of cardiac circadian rhythms, in terms of quantifiable parameters like BP and HR. We also elaborate on the molecular regulators and the molecular cascades along with their specific genetic aspects involved in modulating circadian rhythms, with specific reference to cardiovascu-lar health and cardiovascular diseases. Along with this, we also presented the latest phar-macogenomic and metabolomics markers involved in chronobiological control of the cardiovascu-lar system along with their possible utility in cardiovascular disease diagnosis and therapeutics. Finally, we reviewed the current expert opinions on chronotherapeutic approaches for utilizing the conventional as well as the new pharmacological molecules for antihypertensive chronotherapy.
Kumar Bhavna, Komal Satish Gondkar, Priyanshu Kumar, Uddipak Rai, Manmohan Singhal, Vijay Singh Rana, Neeraj Kumar Sethiya, Samir Bhargava, Mandeep Kumar Arora, Abhijeet Ojha,et al.
Elsevier
Manmohan Singhal, Mohit Agrawal, Kumar Bhavna, Neeraj Kumar Sethiya, Samir Bhargava, Komal Satish Gondkar, Kumud Joshi, Vijay Singh Rana, Jagannath Sahoo, and Mandeep Kumar Arora
Elsevier
Mandeep K. Arora, Ashok Jangra, Deepika Singh, and Ritu Tomar
Bentham Science Publishers Ltd.
Background: A substantial amount of evidence indicates that long-term arsenic exposure leads to various types of pathological complications, especially cognitive dysfunction. Objective: The present study was designed to assess the neuroprotective potential of edaravone (a potent free radical scavenger) against arsenic-induced neurotoxicity in Wistar rats. Methods: Adult male Wistar rats were randomly divided into five groups. Arsenic (20 mg/kg/day; p.o.) and Edaravone (5 and 10 mg/kg/day; i.p.) were administered in different experimental groups for 28 days. Results: The results of various behavioral test paradigms revealed that arsenic caused significant learning and memory deficits, along with anxiety-like behavior. In biochemical analysis, we found marked elevations of oxidative-nitrosative stress (indicated by augmentation of lipid peroxidation and nitrite) and a reduction of glutathione levels in the hippocampus and frontal cortex region of arsenictreated rats. Moreover, arsenic administration caused mitochondrial complexes impairment and reduction of acetylcholinesterase level. On the other hand, chronic treatment with edaravone (10 mg/kg) significantly ameliorated the arsenic-induced behavioral deficits and neurochemical anomalies. Conclusion: This study suggests that edaravone confers neuroprotection against arsenic-induced memory impairment and anxiety-like behavior, which may be attributed to the inhibition of oxidativenitrosative stress and amelioration of cholinergic and mitochondrial functions.
Mohd. Imran, Mandeep Kumar Arora, Anurag Chaudhary, Shah Alam Khan, Mehnaz Kamal, Manal Mutlaq Alshammari, Raghad Mohammad Alharbi, Nuha Abdullah Althomali, Ibrahim Mohammed Alzimam, Abdullah Ayed Alshammari,et al.
MDPI AG
Tuberculosis (TB) is accountable for considerable global morbidity and mortality. Effective TB therapy with multiple drugs completes in about six months. The longer duration of TB therapy challenges patient compliance and contributes to treatment collapse and drug resistance (DR) progress. Therefore, new medications with an innovative mechanism of action are desperately required to shorten the TB therapy’s duration and effective TB control. The mycobacterial membrane protein Large 3 (MmpL3) is a novel, mycobacteria-conserved and recognized promiscuous drug target used in the development of better treatments for multi-drug resistance TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). This article spotlights MmpL3, the clinical studies of its inhibitor (SQ109), and the patent literature. The literature on MmpL3 inhibitors was searched on PubMed and freely available patent databases (Espacenet, USPTO, and PatentScope). SQ109, an analog of ethambutol (EMB), is an established MmpL3 inhibitor and has completed Phase 2b-3 clinical trials. Infectex and Sequella are developing orally active SQ109 in partnership to treat MDR pulmonary TB. SQ109 has demonstrated activity against drug-sensitive (DS) and drug-resistant (DR) Mycobacterium tuberculosis (Mtb) and a synergistic effect with isoniazid (INH), rifampicin (RIF), clofazimine (CFZ), and bedaquiline (BNQ). The combination of SQ109, clofazimine, bedaquiline, and pyrazinamide (PZA) has been patented due to its excellent anti-TB activity against MDR-TB, XDR-TB, and latent-TB. The combinations of SQ109 with other anti-TB drugs (chloroquine, hydroxychloroquine, and sutezolid) have also been claimed in the patent literature. SQ109 is more potent than EMB and could substitute EMB in the intensive stage of TB treatment with the three- or four-drug combination. Developing MmpL3 inhibitors is a promising approach to fighting the challenges associated with DS-TB and DR-TB. The authors foresee MmpL3 inhibitors such as SQ109 as future drugs for TB treatment.
Vardan Gupta, Anchal Garg, Ritu Tomar, and Mandeep Kumar Arora
Bentham Science Publishers Ltd.
Abstract: The vascular endothelium is the innermost lining of blood vessels, which maintains vaso-constriction and vasodilation. Loss of vascular tone is a hallmark for cardiovascular disorders. Nu-merous factors, such as over-activation of the renin-angiotensin-aldosterone system, kinases, growth factors, etc., play a crucial role in the induction and progression of vascular abrasion. Interestingly, dysregulation of these pathways either enhances the intensity of oxidative stress, or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered a key culprit in the pro-gression of vascular endothelial dysfunction. Oxidative stress induced by reactive oxygen and nitro-gen species causes abnormal gene expression, alteration in signal transduction, and the activation of pathways, leading to induction and progression of vascular injury. In addition, numerous antioxidants have been noted to possess promising therapeutic potential in preventing the development of vascular endothelial dysfunction. Therefore, we have focused on current perspectives in oxidative stress sig-nalling to evaluate common biological processes whereby oxidative stress plays a crucial role in the progression of vascular endothelial dysfunction.
Satish Kumar Sharma, Pankaj Bhatt, Syed Mohammed Basheeruddin Asdaq, Mohammed Kanan Alshammari, Abeer Alanazi, Naif Saleh Alrasheedi, Bader Abdullah Alrashdi, Saad Saleh Alyami, Bshayer Hamdan Alhazmi, Perwaiz Alam,et al.
Elsevier BV
Vrish Dhwaj Ashwlayan, Chanchal Antlash, Mohd. Imran, Syed Mohammed Basheeruddin Asdaq, Mohammed Kanan Alshammari, Marwa Alomani, Eman Alzahrani, Divya Sharma, Ritu Tomar, and Mandeep Kumar Arora
Elsevier BV
Mandeep Kumar Arora, Anish Ratra, Syed Mohammed Basheeruddin Asdaq, Ali A. Alshamrani, Abdulkhaliq J. Alsalman, Mehnaz Kamal, Ritu Tomar, Jagannath Sahoo, Jangra Ashok, and Mohd Imran
MDPI AG
Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 μL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative–nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.
Mandeep Kumar Arora, Parul Grover, Syed Mohammed Basheeruddin Asdaq, Lovekesh Mehta, Ritu Tomar, Mohd. Imran, Anuj Pathak, Ashok Jangra, Jagannath Sahoo, Abdulhakeem S. Alamri,et al.
Elsevier BV
Ashok Jangra, Mandeep Kumar Arora, Anglina Kisku, and Sonal Sharma
Springer Science and Business Media LLC
Ashok Jangra, Vaishali Chadha, Dinesh Kumar, Vipin Kumar, and Mandeep K Arora
Elsevier BV
Mohd. Imran, Mandeep Kumar Arora, Syed Mohammed Basheeruddin Asdaq, Shah Alam Khan, Saleh I. Alaqel, Mohammed Kanan Alshammari, Mohammed M. Alshehri, Ahmed Subeh Alshrari, Alreshidi Mateq Ali, Ahmed Muteb Al-shammeri,et al.
MDPI AG
The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.
Anchal Garg, Vardan Gupta, Ritu Tomar, and Mandeep Kumar Arora
Bangladesh Journals Online (JOL)
Vascular endothelial dysfunction is characterized by apoptosis of endothelial cells, an imbalance between vasoconstrictory and vasodilatory substances, the imbalance between ROS and antioxidants, vascular remodeling, loss of vascular integrity which leads to an increased risk of cardiovascular complications. To date, no therapeutic intervention is available as a promising agent. This may be due to a poor understanding of the underlying mechanism involved in vascular endothelial dysfunction in the pathogenesis. Animal models sharing identical features as that of humans are paramount to understand fundamental physiology, mechanism and to explore new targets for developing therapeutic agents. Thus, it becomes mandatory to re-explore the available animal models for a better understanding of molecular pathways involving vascular endothelial dysfunction. The purpose of this paper is to review different models for vascular endothelial dysfunction to the outlook for developing new drugs to treat vascular endothelial dysfunction.
M. Arora, Anglina Kisku and A. Jangra
INTRODUCTION: Mangiferin (MGF), a xanthonoid polyphenol, confers neuroprotection via combating oxidative stress and inflammation. The current investigation aimed to assess the neuroprotective potential of MGF on behavioral and neurochemical anomalies evoked by administration of quinolinic acid (QA) through intrastriatal injection in male Wistar rats and to reveal the associated mechanisms. MATERIALS AND METHODS: QA (300 nm/4 μl saline) was administered intracerebroventricular in the striatum (unilaterally) once. Thereafter, MGF 20 and 40 mg/kg (peroral) was administered to the animals for 21 days. RESULTS: QA administration caused marked alteration in motor activity (rotatod), footprint analysis, and cognitive function (Morris water maze test, and novel object recognition test). Furthermore, oxido-nitrosative stress (increased nitrite content, lipid peroxidation, with reduction of GSH), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in hippocampus and striatal region of QA-treated rats in comparison to normal control. Pro inflammatory mediators (tumor necrosis factor-alpha TNF-α and interleukin-1β) were noted to increase in the hippocampus and striatum of QA-treated rats. In addition, we observed BDNF depletion in both the hippocampus and striatum of QA-treated animals. MGF treatment significantly ameliorated memory and motor deficits in QA-administered rats. Moreover, MGF treatment (40 mg/kg) restored the GSH level and reduced the MDA, nitrite level, and pro-inflammatory cytokines in striatum and hippocampus. Furthermore, QA-induced cholinergic dysfunction (AChE), BDNF depletion and mitochondrial impairment were found to be ameliorated by MGF treatment. CONCLUSION: The results suggest that MGF offers the neuroprotective potential that may be a promising pharmacological approach to ameliorate cognitive deficits associated with neurodegeneration.
Mandeep Kumar Arora, Yogesh Sarup, Ritu Tomar, Mary Singh, and Puspendra Kumar
Informa UK Limited
ABSTRACT This study investigated the effect of Aloe vera in diabetes-induced nephropathy in rats. As diabetes-associated hyperlipidemia and oxidative stress have been implicated in the pathogenesis of diabetic nephropathy, we evaluated the protective effect of whole leaf extract of Aloe vera on the basis of its hypolipidemic and antioxidative property. Aloe vera (300 mg/kg orally) has been noted to possess renoprotective effect in experimental diabetic nephropathy. However, its mechanism is not fully understood. Rats were administered streptozotocin (STZ) (55 mg/kg intraperitoneally once) to induce experimental diabetes mellitus. The development of diabetic nephropathy was assessed biochemically and histologically. In addition, the diabetes-induced lipid profile and renal oxidative stress were assessed. The single administration of STZ produced diabetes, which induced renal oxidative stress, altered the lipid profile, and subsequently produced nephropathy in eight weeks by increasing serum creatinine, blood urea nitrogen, proteinuria, and glomerular damage. Treatment with Aloe vera (300 mg/kg/day orally) was noted to be more effective against the diabetes-induced nephropathy and renal oxidative stress as compared to lisinopril (1 mg/kg/day orally), a reference agent. It may be concluded that diabetes-induced oxidative stress and lipid alterations may be accountable for the induction of nephropathy in diabetic rats. The treatment with Aloe vera (300 mg/kg/day orally) may have prevented the development of diabetes-induced nephropathy by reducing lipid alteration, decreasing renal oxidative stress, and providing direct renoprotective action.
Mandeep Arora and Umesh Singh
Bentham Science Publishers Ltd.
Excessive production of reactive oxygen species is an important mechanism underlying the pathogenesis of diabetes associated macrovascular and microvascular complications including diabetic nephropathy. Diabetic nephropathy is characterized by glomerular enlargement, early albuminuria and progressive glomerulosclerosis. The pathogenesis of diabetic nephropathy is multi-factorial and the precise mechanisms are unclear. Hyperglycemia-mediated dysregulation of various pathways either enhances the intensity of oxidative stress or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered as a central mediator in progression of nephropathy in patients with diabetes. In this review, we have focused on current perspectives in oxidative stress signaling to determine common biological processes whereby diabetes-induced oxidative stress plays a central role in progression of diabetic nephropathy.