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Arunkumar Subramanian,1 Afrarahamed J,1 Tamilanban T,1,2 Vinoth Kumarasamy,3 M Yasmin Begum,4 Mahendran Sekar,5 Vetriselvan Subramaniyan,6 Ling Shing Wong,7 Adel Al Fatease4 1Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, India; 2Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, Malaysia; 3Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia; 4Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 5School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 6Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, Malaysia; 7Faculty of Health and Life Sciences, INTI International University, Nilai, MalaysiaCorrespondence: Tamilanban T; Vinoth Kumarasamy, Email tamilant@srmist.edu.in; vinoth@ukm.edu.myAbstract: Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and ulcerative colitis, represents a complex and growing global health issue with a multifaceted origin. This review delves into the intricate relationship between gut microbiota, autophagy, and the development of IBD. The gut microbiota, a diverse community of microorganisms, plays a vital role in maintaining gut health, while imbalances in this microbial community, known as dysbiosis, are linked to IBD. Autophagy, a process by which cells recycle their components, is essential for gut homeostasis and the regulation of immune responses. When autophagy is impaired and dysbiosis occurs, they individually contribute to IBD, with their combined impact intensifying inflammation. The interconnectedness of gut microbiota, autophagy, and the host’s immune system is central to the onset of IBD. The review also examines how diet influences gut microbiota and its subsequent effects on IBD. It highlights the therapeutic potential of targeting the microbiota and modulating autophagic pathways as treatment strategies for IBD. Understanding these interactions could lead to personalized therapies within the rapidly advancing fields of microbiome research and immunology. Keywords: inflammatory bowel disease, gut microbiota, autophagy, Crohn’s disease, ulcerative colitis

Amrita Muralikrishnan,1 Mahendran Sekar,1 Vinoth Kumarasamy,2 Siew Hua Gan,1 Subban Ravi,3 Vetriselvan Subramaniyan,4 Ling Shing Wong,5 Yuan Seng Wu,6 Farrah Syazana Khattulanuar,7 Nur Najihah Izzati Mat Rani7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 4Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor 47500, Malaysia; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia, Email mahendran.sekar@moansh.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Decursin is a pyranocoumarin compounds which are rare secondary metabolic plant products, isolated from the roots of Angelica gigas (A. gigas). The native Korean species Angelica gigas Nakai (AGN) is widely used as a remedy for a variety of medical conditions including hematopoiesis, improving women’s circulation, as sedatives, analgesics and tonic. It is unique because of the presence of substantial amounts of pyranocoumarins including decursin, decursinol, and decursinol angelate. In this review, we provide a comprehensive insight into the distribution, morphology, and chemical composition of A. gigas. A detailed discussion regarding the biological applications of decursin based on the literature retrieved from PubMed, ScienceDirect, Scopus, and Google Scholar from 2000 to the present has been discussed. Both in vitro and in vivo studies have demonstrated that decursin has potential neuroprotective, anti-inflammatory, anti-melanogenic, anti-angiogenic, antioxidant, and anti-visceral properties. Mechanistic findings establish its significance in regulating important signalling pathways, triggering apoptosis, and preventing metastasis in different cancer types. The review additionally addressed the isolation methods, biosynthesis, physiochemical characteristics, toxicity and pharmacokinetic profile of decursin. The present state of clinical studies including A. gigas is investigated, emphasizing its advancements and possibilities in the field of translational medicine. Keywords: decursin, Angelica gigas, pyranocoumarins, biosynthesis, pharmacology

Aathira Sujathan Nair,1 Mahendran Sekar,1 Siew Hua Gan,1 Vinoth Kumarasamy,2 Vetriselvan Subramaniyan,3 Yuan Seng Wu,4 Nur Najihah Izzati Mat Rani,5 Subban Ravi,6 Ling Shing Wong7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 4Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia, Email mahendran.sekar@monash.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy. Keywords: lawsone, Lawsonia inermis, henna, antitumor, antioxidant, anti-inflammatory, antimicrobial

Muhamad Azrul Amir Yusri,1 Mahendran Sekar,2,3 Ling Shing Wong,4 Siew Hua Gan,2 Subban Ravi,5 Vetriselvan Subramaniyan,6 Nur Najihah Izzati Mat Rani,7 Kumarappan Chidambaram,8 M Yasmin Begum,9 Mohankumar Ramar,10 Sher Zaman Safi,11 Siddharthan Selvaraj,12 Yuan Seng Wu,13 Palanisamy Revathy,14 Shivkanya Fuloria,15 Neeraj Kumar Fuloria,15 Pei Teng Lum,1 Sinouvassane Djearamane16 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India; 4Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia; 5Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 6Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, Malaysia; 8Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia; 10Department of Surgical Research, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, USA; 11Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia; 12Faculty of Dentistry, AIMST University, Bedong, Kedah, Malaysia; 13Department of Biological Sciences and Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, Malaysia; 14Department of Computer Applications, Gobi Arts & Science College, Gobichettipalayam, Tamil Nadu, India; 15Faculty of Pharmacy, AIMST University, Bedong, Kedah, Malaysia; 16Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, MalaysiaCorrespondence: Ling Shing Wong, Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia, Tel +6014 3034057, Email lingshing.wong@newinti.edu.my Sinouvassane Djearamane, Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, Malaysia, Tel +6016 4037685, Email biochsinouvas07@gmail.comAbstract: Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.Graphical Abstract: Keywords: celastrol, memory impairment, neuroprotection, drug discovery, natural products

Naurah Nabihah Nasir,1 Mahendran Sekar,2,3 Subban Ravi,4 Ling Shing Wong,5 Sreenivas Patro Sisinthy,6 Siew Hua Gan,2 Vetriselvan Subramaniyan,7 Kumarappan Chidambaram,8 Nur Najihah Izzati Mat Rani,6 M Yasmin Begum,9 Mohankumar Ramar,10 Sher Zaman Safi,11 Siddharthan Selvaraj,12 Senthil Kumar Chinna Maruthu,13 Shivkanya Fuloria,14 Neeraj Kumar Fuloria,14 Pei Teng Lum,1 Sinouvassane Djearamane15 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, 47500, Malaysia; 3Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Saveetha University, Chennai, Tamil Nadu, 600077, India; 4Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 7Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, Malaysia; 8Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia; 9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, 61421, Saudi Arabia; 10Department of Surgical Research, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, 02903, USA; 11Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor, 42610, Malaysia; 12Faculty of Dentistry, AIMST University, Bedong, Kedah, 08100, Malaysia; 13Department of Pharmacology, Karpagam College of Pharmacy, Coimbatore, Tamilnadu, 641032, India; 14Faculty of Pharmacy, AIMST University, Bedong, Kedah, 08100, Malaysia; 15Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, 31900, MalaysiaCorrespondence: Ling Shing Wong, Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia, Tel +6014 – 3034057, Email lingshing.wong@newinti.edu.my Sinouvassane Djearamane, Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, 31900, Perak, Malaysia, Tel +6016 – 4037685, Email biochsinouvas07@gmail.comAbstract: Streptonigrin is an aminoquinone alkaloid isolated from Streptomyces flocculus and is gaining attention as a drug molecule owing to its potential antitumor and antibiotic effects. It was previously used as an anticancer drug but has been discontinued because of its toxic effects. However, according to the most recent studies, the toxicity of streptonigrin and its structurally modified derivatives has been reduced while maintaining their potential pharmacological action at lower concentrations. To date, many investigations have been conducted on this molecule and its derivatives to determine the most effective molecule with low toxicity to enable new drug discovery. Therefore, the main objective of this study is to provide a comprehensive review and to discuss the prospects for streptonigrin and its derived compounds, which may boost the molecule as a highly interesting target molecule for new drug design, development and therapy. To complete this review, relevant literature was collected from several scientific databases, including Google Scholar, PubMed, Scopus and ScienceDirect. Following a complete screening, the obtained information is summarized in the present review to provide a good reference and accelerate the development and utilization of streptonigrin and its derivatives as pharmaceuticals.Graphical Abstract: Keywords: streptonigrin, chemistry, biosynthesis, pharmacology, anticancer, antibacterial

Siddharthan Selvaraj,1,2 Nyi Nyi Naing,1 Nadiah Wan-Arfah,3 Sinouvassane Djearamane,4 Ling Shing Wong,5 Vetriselvan Subramaniyan,6 Neeraj Kumar Fuloria,7 Mahendran Sekar,8 Shivkanya Fuloria,7 Mauro Henrique Nogueira Guimarães de Abreu9 1Faculty of Medicine, Medical Campus, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, 20400, Malaysia; 2Faculty of Dentistry, AIMST University, Bedong, Kedah, 08100, Malaysia; 3Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, 20400, Malaysia; 4Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Kampar, Perak, 31900, Malaysia; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jen jarom, Selangor, 42610, Malaysia; 7Faculty of Pharmacy, AIMST University, Bedong, Kedah, 08100, Malaysia; 8Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 9School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, CEP 31270- 901, BrazilCorrespondence: Nyi Nyi Naing; Sinouvassane Djearamane, Email syedhatim@unisza.edu.my; sinouvassane@utar.edu.myIntroduction: Oral conditions exist worldwide, and are related with astounding morbidity. Indian adults’ incidence of mild and moderate periodontal conditions was nearly 25%, while about 19% of adults experience severe periodontitis.Objective: The aim of this study was to analyse epidemiological factors of periodontal disease among a south Indian population based on the role of sociodemographic factors, habitual factors and set of oral health knowledge, attitude, and behaviour measures.Methods: A sample of 288 participants above 18 years of age residing in Tamil Nadu, India took part in this cross-sectional study. Based on WHO criteria, periodontal disease was measured in our study. Age, ethnicity, smoking, education, and oral health behavior were found to be the covariates. Ordinal logistic regression analysis using R version 3.6.1 was utilized to study the various factors that influence periodontal disease among south Indian adults.Results: Various demographic factors such as age between 25 and 34 years (AOR = 2.25; 95% CI 1.14– 4.55), 35– 44 years (AOR = 1.80; 95% CI 0.89– 3.64), ≥ 45 years old (AOR = 2.89; 95% CI 1.41– 6.01), ethnicity (AOR = 2.71; 95% CI 1.25– 5.81), smoking (AOR = 0.38; 95% CI 0.16– 0.65), primary level education (AOR = 0.07; 95% CI 0.01– 0.50) high school level education (AOR = 0.06; 95% CI 0.01– 0.27), university level education (AOR = 0.08; 95% CI 0.01– 0.36) and an individual’s oral health behavior (AOR = 0.59; 95% CI 0.32– 1.08) were found to be related with periodontal disease among the south Indian population. The maximum log likelihood residual deviance value was 645.94 in the final model.Conclusion: Based on our epidemiological findings, sociodemographic, habitual factors and oral health behavior play a vital role in an individual’s periodontal status among south Indian adults. An epidemiological model derived from the factors from our study will help to bring better understanding of the disease and to implement various preventive strategies to eliminate the causative factors.Keywords: periodontal disease, epidemiology, modelling, socio-demography, habits