Browsing by Author "Sweilam, Sherouk Hussein"

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Alkaloid-based modulators of the PI3K/Akt/mTOR pathway for cancer therapy: Understandings from pharmacological point of view
(Scopus, 2024) Mokhfi, Fatima Zohra; Amin, Md Al; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Arjun, Uppuluri Varuna Naga Venkata; Gupta, Jeetendra Kumar; Vallamkonda, Bhaskar; Balakrishnan, Anitha; Challa, Manjula; Singh, Jyoti; Prasad, P. Dharani; Ali, Syed Salman; Ahmad, Irfan; Doukani, Koula; Emran, Talha Bin
This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.
Alkaloid-based Modulators of the PI3K/AKT/MTOR Pathway for Cancer Therapy: Understandings from Pharmacological Point of View
(Elsevier, 2024-10-01) Mokhfi, Fatima Zohra; Amin, Md Al; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Arjun, Uppuluri Varuna Naga Venkata; Gupta, Jeetendra Kumar; Vallamkonda, Bhaskar; Balakrishnan, Anitha; Challa, Manjula; Singh, Jyoti; Prasad, Dharani; Ali, Syed Salman; Ahmad, Irfan; Doukani, Koula; Emran, Talha Bin
This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.
Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders
(Springer Nature, 2024-08-15) Faysal, Md.; Dehbia, Zerrouki; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Haque, M. Akiful; Kumar, Kusuma Praveen; Chakole, Rita D.; Shelke, Satish P.; Sirikonda, Swapna; Nafady, Mohamed H.; Khan, Sharuk L.; Nainu, Firzan; Ahmad, Irfan; Emran, Talha Bin
Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.
Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects
(2024-06-01) Faysal, Md.; Dehbia, Zerrouki; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Akiful Haque, M.; Kumar, Kusuma Praveen; D. Chakole, Rita; P. Shelke, Satish; Sirikonda, Swapna; H. Nafady, Mohamed; L. Khan, Sharuk; Nainu, Firzan; Ahmad, Irfan; Bin Emran, Talha
Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.
Gastroprotective Efficacy of North African Medicinal Plants: A Review on Their Therapeutic Potential for Peptic Ulcers
(2024-10-22) Cherrada, Nezar; Chemsa, Ahmed Elkhalifa; Gheraissa, Noura; Laib, Ibtissam; Gueboudji, Zakia; EL-Shazly, Mohamed; Zaater, Abdelmalek; Abid, Asma; Sweilam, Sherouk Hussein; Emran, Talha Bin; Nani, Sadok; Benamor, Bilal; Amara, Djilani Ghemam; Victor Atoki, Ayomide; Messaoudi, Mohammed
Peptic ulcer disease remains a prevalent gastrointestinal disorder worldwide. Current treatments often have limitations, sparking interest in alternative therapies from medicinal plants. This review examines the gastroprotective potential of 54 North African medicinal plants against peptic ulcers. An extensive literature search was conducted, focusing on plants with preclinical and clinical evidence of anti-ulcer efficacy and documented use in North African traditional medicine. The review identified several promising plant species, such as licorice (Glycyrrhiza glabra), chamomile (Matricaria chamomilla), olive (Olea europaea), pomegranate (Punica granatum), Aloe vera, and black seed (Nigella sativa), along with their bioactive constituents, including flavonoids, tannins, and terpenoids. These compounds exhibit gastroprotective properties through multiple mechanisms, such as enhancing the gastric mucosal barrier, inhibiting acid secretion, displaying antioxidant and anti-inflammatory effects, promoting ulcer healing, and combating Helicobacter pylori infection. The evidence presented includes in vitro assays, animal models, and some clinical studies. While many of the 53 plants reviewed demonstrated significant anti-ulcer effects compared to standard drugs, further clinical research is needed to establish efficacy and safety in humans. The synergistic actions of phytochemical mixtures in medicinal plant extracts likely contribute to their therapeutic potential. This review highlights the role these North African medicinal plants may play in the prevention and treatment of peptic ulcers and identifies promising candidates for further research and development of evidence-based botanical therapies.
In Silico Investigation and Potential Therapeutic Approaches of Natural Products for COVID-19
(Daffodil International University, 2022-08-22) Rahman, Md. Mominur; Islam, Md. Rezaul; Akash, Shopnil; Mim, Sadia Afsana; Rahaman, Md. Saidur; Emran, Talha Bin; Akkol, Esra Küpeli; Sharma, Rohit; Alhumaydhi, Fahad A.; Sweilam, Sherouk Hussein; Hossain, Md. Emon; Ray, Tanmay Kumar; Sultana, Sharifa; Ahmed, Muniruddin; Sobarzo-Sa´nchez, Eduardo; Wilairatana, Polrat
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners’ safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics’ data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.
Polyphenols in Wound Healing: Unlocking Prospects with Clinical Applications
(Springer Nature, 2024-10-15) Utpal, Biswajit Kumar; Sutradhar, Baishakhi; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Panigrahy, Uttam Prasad; Urs, Deepadarshan; Fatima, Ayesha Farhath; Nallasivan, Kumar; Chhabra, Gurmeet Singh; Sayeed, Mohammed; Alshehri, Mohammed Ali; Rab, Safia Obaidur; Khan, Sharuk L.; Emran, Talha Bin
Wound healing is a multifaceted, complex process that factors like aging, metabolic diseases, and infections may influence. The potentiality of polyphenols, natural compounds, has shown anti-inflammatory and antimicrobial properties in promoting wound healing and their potential applications in wound management. The studies reviewed indicate that polyphenols have multiple mechanisms that promote wound healing. This involves enhancing antioxidant defenses, reducing oxidative stress, modulating inflammatory responses, improving healing times, reducing infection rates, and enhancing tissue regeneration in clinical trials and in vivo and in vitro studies. Polyphenols have been proven to be effective in managing hard-to-heal wounds, especially in diabetic and elderly populations. Polyphenols have shown significant benefits in promoting angiogenesis and stimulating collagen synthesis. Polyphenol treatment has been demonstrated to have therapeutic effects in wound healing and chronic wound management. Their ability to regulate key healing processes makes them suitable for new wound care products and treatments. Future research should enhance formulations and delivery methods to optimize polyphenols' bioavailability and therapeutic efficacy in wound management approaches.
Polyphenols Targeting Oxidative Stress in Spinal Cord Injury
(Daffodil International University, 2022-08-22) Islam, Fahadul; Bepary, Sristy; Nafady, Mohamed H.; Islam, Md. Rezaul; Emran, Talha Bin; Sultana, Sharifa; Huq, Md. Amdadul; Mitra, Saikat; Chopra, Hitesh; Sharma, Rohit; Sweilam, Sherouk Hussein; Khandaker, Mayeen Uddin; Idris, Abubakr M.
A spinal cord injury (SCI) occurs when the spinal cord is deteriorated or traumatized, leading to motor and sensory functions lost even totally or partially. An imbalance within the generation of reactive oxygen species and antioxidant defense levels results in oxidative stress (OS) and neuroinflammation. After SCI, OS and occurring pathways of inflammations are significant strenuous drivers of cross-linked dysregulated pathways. It emphasizes the significance of multitarget therapy in combating SCI consequences. Polyphenols, which are secondary metabolites originating from plants, have the promise to be used as alternative therapeutic agents to treat SCI. Secondary metabolites have activity on neuroinflammatory, neuronal OS, and extrinsic axonal dysregulated pathways during the early stages of SCI. Experimental and clinical investigations have noted the possible importance of phenolic compounds as important phytochemicals in moderating upstream dysregulated OS/inflammatory signaling mediators and axonal regeneration’s extrinsic pathways after the SCI probable significance of phenolic compounds as important phytochemicals in mediating upstream dysregulated OS/inflammatory signaling mediators. Furthermore, combining polyphenols could be a way to lessen the effects of SCI.
Resveratrol and Neuroprotection
(Daffodil International University, 2022-05-12) Islam, Fahadul; Nafady, Mohamed H.; Islam, Md. Rezaul; Saha, Susmita; Rashid, Salma; Akter, Aklima; Rashid, Md. Harun‑ Or‑; Akhtar, Muhammad Furqan; Perveen, Asma; Ashraf, Ghulam Md.; Rahman, Md. Habibur; Sweilam, Sherouk Hussein
Alzheimer’s disease (AD) is the most common cause of dementia and cognitive impairment; yet, there is currently no treatment. A buildup of Aβ, tau protein phosphorylation, oxidative stress, and inflammation in AD is pathogenic. The accumulation of amyloid-beta (Aβ) peptides in these neurocognitive areas is a significant characteristic of the disease. Therefore, inhibiting Aβ peptide aggregation has been proposed as the critical therapeutic approach for AD treatment. Resveratrol has been demonstrated in multiple studies to have a neuroprotective, anti-inflammatory, and antioxidant characteristic and the ability to minimize Aβ peptides aggregation and toxicity in the hippocampus of Alzheimer’s patients, stimulating neurogenesis and inhibiting hippocampal degeneration. Furthermore, resveratrol’s antioxidant effect promotes neuronal development by activating the silent information regulator-1 (SIRT1), which can protect against the detrimental effects of oxidative stress. Resveratrol-induced SIRT1 activation is becoming more crucial in developing novel therapeutic options for AD and other diseases that have neurodegenerative characteristics. This review highlighted a better knowledge of resveratrol’s mechanism of action and its promising therapeutic efficacy in treating AD. We also highlighted
Resveratrol: A Natural Compound Targeting the PI3K/Akt/mTOR Pathway in Neurological Diseases
(Springer Nature, 2024-11-23) Biswajit Kumar Utpal, Biswajit Kumar; Mokhfi, Fatima Zohra; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Gupta, Jeetendra Kumar; Kareemulla, Shaik; Darwin, Ronald; Rao, A. Anka; Kumar, Voleti Vijaya; Pavankumar Krosuri, Pavankumar; Prasad, Dharani; Khan, Sharukh L.; Roy, Sajib Chandra; Rab, Safia Obaidur; Alshehri, Mohammed Ali; Emran, Talha Bin
Neurological diseases (NDs), including neurodegenerative disorders and acute injuries, are a significant global health concern. The PI3K/Akt/mTOR pathway, a crucial signaling cascade, is responsible for the survival of cells, proliferation, and metabolism. Dysregulation of this pathway has been linked to neurological conditions, indicating its potential as a vital target for therapeutic approaches. Resveratrol (RSV), a natural compound found in berries, peanuts, and red grapes, has antioxidant, anti-cancer, and anti-inflammatory effects. Its ability to modulate the PI3K/Akt/mTOR pathway has been interesting in NDs. Studies have shown that RSV can activate the PI3K/Akt pathway, promoting cell survival and inhibiting apoptosis of neuronal cells. Its impact on mTOR, a downstream effector of Akt, further contributes to its neuroprotective effects. RSV’s ability to restore autophagic flux presents a promising avenue for therapeutic intervention. Its anti-inflammatory properties suppress inflammatory responses by inhibiting key signaling molecules within the pathway. Additionally, RSV’s role in enhancing mitochondrial function contributes to its neuroprotective profile. This study highlights RSV’s potential as a multifaceted therapeutic agent in NDs, specifically by PI3K/Akt/mTOR pathway modulation. Additional investigation is required to optimize its therapeutic capacity in diverse neurological conditions.
Tacrine Derivatives in Neurological Disorders
(Daffodil International University, 2022-08-18) Mitra, Saikat; Muni, Maniza; Shawon, Nusrat Jahan; Das, Rajib; Emran, Talha Bin; Sharma, Rohit; Chandran, Deepak; Islam, Fahadul; Hossain, Md. Jamal; Safi, Sher Zaman; Sweilam, Sherouk Hussein
Tacrine is a drug used in the treatment of Alzheimer’s disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer’s disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers’ interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer’s disease, as well as other neurological disorders like Parkinson’s disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
Targeting Neurological Disorders with Stilbenes: Bridging the Preclinical-Clinical Gap
(Scopus, 2024-10-10) Begh, Md. Zamshed Alam; Khan, Jishan; Zehravi, Mehrukh; Sweilam, Sherouk Hussein; Raja, A. Dinesh; Muthukumar, A.; Haque, M Akiful; Kar, Nihar Ranjan; Singh, Laliteshwar Pratap; Priya, B. Dharani; Alshehri, Mohammed Ali; Ahmad, Irfan; Kang, Sojin; Moon, Seungjoon; Park, Moon Nyeo; Emran, Talha Bin; Kim, Bonglee
Neurological disorders (NDs) encompass a range of debilitating conditions that affect the nervous system, including prevalent illnesses such as Alzheimer's disease, Parkinson's disease, and ischemic stroke. Despite significant ongoing studies, effective therapeutic strategies to halt or slow down the progression of these illnesses are still lacking. Stilbenes, a class of natural polyphenols, have shown potential as candidates for therapeutic strategies due to their capacity to protect the nervous system. Preclinical studies have provided strong evidence that stilbenes can regulate many cellular pathways implicated in neurodegeneration, with resveratrol being a well-studied compound that has shown the ability to reduce oxidative damage, promote neurogenesis, and enhance mitochondrial function - crucial for maintaining brain health. In preclinical animal models, initial research has also shown promise in additional substances such as piceatannol and pterostilbene. Furthermore, clinical studies have explored the therapeutic benefits of stilbenes in NDs. Despite promising results in preclinical research, the use of stilbenes in clinical trials is currently limited, with most studies focusing on resveratrol. Although several clinical studies have demonstrated the beneficial impact of resveratrol supplementation on brain health and degenerative consequences, other investigations have yielded ambiguous findings, underscoring the urgent need for more comprehensive and precisely planned clinical research. This study delves into the potential benefits of stilbenes as neuroprotective agents for NDs. It emphasizes the need for more clinical research to enhance our understanding of their therapeutic effectiveness in specific patient groups.
The Impact of Mucormycosis (Black Fungus) on SARS-CoV-2-Infected Patients
(Daffodil International University, 22-08-19) Islam, Md. Rezaul; Rahman, Md. Mominur; Ahasan, Md. Tanjimul; Sarkar, Nadia; Akash, Shopnil; Islam, Mahfuzul; Islam, Fahadul; Aktar, Most. Nazmin; Saeed, Mohd; Harun-Or-Rashid, Md.; Hosain, Md. Kawsar; Rahaman, Md. Saidur; Afroz, Sadia; Bibi, Shabana; Rahman, Md. Habibur; Sweilam, Sherouk Hussein
The emergence of various diseases during the COVID-19 pandemic made health workers more attentive, and one of the new pathogens is the black fungus (mucormycosis). As a result, millions of lives have already been lost. As a result of the mutation, the virus is constantly changing its traits, including the rate of disease transmission, virulence, pathogenesis, and clinical signs. A recent analysis revealed that some COVID-19 patients were also coinfected with a fungal disease called mucormycosis (black fungus). India has already categorized the COVID-19 patient black fungus outbreak as an epidemic. Only a few reports are observed in other countries. The immune system is weakened by COVID-19 medication, rendering it more prone to illnesses like black fungus (mucormycosis). COVID-19, which is caused by a B.1.617 strain of the SARS-CoV-2 virus, has been circulating in India since April 2021. Mucormycosis is a rare fungal infection induced by exposure to a fungus called mucormycete. The most typically implicated genera are Mucor rhyzuprhizopusdia and Cunninghamella. Mucormycosis is also known as zygomycosis. The main causes of infection are soil, dumping sites, ancient building walls, and other sources of infection (reservoir words “mucormycosis” and “zygomycosis” are occasionally interchanged). Zygomycota, on the other hand, has been identified as polyphyletic and is not currently included in fungal classification systems; also, zygomycosis includes Entomophthorales, but mucormycosis does not. This current review will be focused on the etiology and virulence factors of COVID-19/mucormycosis coinfections in COVID-19-associated mucormycosis patients, as well as their prevalence, diagnosis, and treatment.