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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

Nurul Amirah Mohd Zaid,1,* Mahendran Sekar,1,* Srinivasa Reddy Bonam,2,* Siew Hua Gan,3 Pei Teng Lum,1 M Yasmin Begum,4 Nur Najihah Izzati Mat Rani,5 Jaishree Vaijanathappa,6 Yuan Seng Wu,7,8 Vetriselvan Subramaniyan,9 Neeraj Kumar Fuloria,10 Shivkanya Fuloria10 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Malaysia; 2Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 3School of Pharmacy, Monash University Malaysia, Selangor Darul Ehsan, 47500, Malaysia; 4Department of Pharmaceutics, College of Pharmacy, King Khalid University (KKU), Asir-Abha, 61421, Saudi Arabia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Malaysia; 6Faculty of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Vacoas-Phoenix, Mauritius; 7Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 8Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 9Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 10Faculty of Pharmacy, AIMST University, Kedah, 08100, Malaysia*These authors contributed equally to this workCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, 30450, Perak, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.Keywords: natural products, skin disorder, dermatitis, psoriasis, skin cancer, anti-inflammatory, drug delivery

Mohd Nasarudin Watroly,1 Mahendran Sekar,1 Shivkanya Fuloria,2 Siew Hua Gan,3 Srikanth Jeyabalan,4 Yuan Seng Wu,5,6 Vetriselvan Subramaniyan,7 Kathiresan V Sathasivam,8 Subban Ravi,9 Nur Najihah Izzati Mat Rani,10 Pei Teng Lum,1 Jaishree Vaijanathappa,11 Dhanalekshmi Unnikrishnan Meenakshi,12 Shankar Mani,13 Neeraj Kumar Fuloria2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 2Faculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 3School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, 47500, Malaysia; 4Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamil Nadu, 600116, India; 5Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 6Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, 47500, Malaysia; 7Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 8Faculty of Applied Science & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, Malaysia; 9Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 640 021, India; 10Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, 30450, Malaysia; 11Department of Pharmaceutical Chemistry, School of Life Sciences, JSS Academy of Higher Education and Research Mauritius, Vacoas, Mauritius; 12College of Pharmacy, National University of Science and Technology, Muscat, 130, Oman; 13Department of Pharmaceutical Chemistry, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, 571418, IndiaCorrespondence: Neeraj Kumar Fuloria; Shivkanya FuloriaFaculty of Pharmacy & Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah, 08100, MalaysiaTel +60 16 4037685; +60 14 3034057Email neerajkumar@aimst.edu.my; shivkanya_fuloria@aimst.edu.myAbstract: Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin’s phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin’s biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski’s rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin’s isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.Keywords: Rubiadin, Rubia cordifolia, biosynthesis, physicochemical properties, anticancer, pharmacology

Nur Sakinah Muhamad Fadzil,1 Mahendran Sekar,1 Siew Hua Gan,2 Srinivasa Reddy Bonam,3 Yuan Seng Wu,4 Jaishree Vaijanathappa,5 Subban Ravi,6 Pei Teng Lum,1 Shivsharan B Dhadde7 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; 3Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 4Department of Biochemistry, School of Medicine, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, Selangor, Malaysia; 5Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru, Karnataka, India; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7D.S.T.S. Mandal’s College of Pharmacy, Solapur, Maharashtra, IndiaCorrespondence: Mahendran SekarDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, No. 3 Jalan Greentown, Ipoh, 30450, Perak, MalaysiaTel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski’s rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.Keywords: swertiamarin, Enicostemma littorale, biosynthesis, metabolic pathway, molecular targets, inflammatory cytokines

Introduction: Bioactive compounds from plants have potential antimicrobial activity. The aim of this in vitro study was to evaluate the antimicrobial efficacy of curcumin, allicin, gingerol and cinnamon compared to 4% sodium hypochlorite (NaOCl) against Enterococcus faecalis and its biofilm. Methods: The dry herbal compounds were diluted with dimethyl sulfoxide (DMSO). Antimicrobial activity was evaluated using agar diffusion test, minimum inhibitory concentration (MIC) assay, minimum bactericidal concentration (MBC) test, time kill study, and biofilm susceptibility assay. The zone of inhibition (ZOI) was determined using agar diffusion test on Muller Hinton (MH) agar plates. MIC was evaluated using the tube dilution method. Root canals of extracted human anterior teeth were instrumented, split into two halves, autoclaved, and incubated with brain heart infusion broth containing E. faecalis for 21 days to form a biofilm. The susceptibility of the biofilm to the test solutions was evaluated by counting bacterial colonies on MH agar. Results: NaOCl exhibited potent antimicrobial activity under all tested parameters. Allicin showed a significantly greater ZOI, while curcumin showed the least MIC among the tested herbal extracts (P0.05). Gingerol and cinnamon were significantly superior to the other groups killing E. faecalis within 4-4.2 min (P0.05). Conclusion: NaOCl emerged as the most efficacious antibacterial agent and all herbal extracts showed significant antibacterial activity against E. faecalis.

Introduction: Ethylenediaminetetraacetic acid (EDTA), a widely used chelating agent, compromises the bond strength of resin-based sealers when used as a final irrigating solution. Hence, the push-out bond strength of AH Plus, a resin-based sealer, was analyzed when gallic acid, "a chelator" was used as a last irrigating solution. Methods: Forty human single-rooted teeth were accessed and randomly assigned into 4 groups (n = 10): EA (17% EDTA), MA (7% maleic acid), GA (10% gallic acid), and SA (saline). After irrigation, the root canals were coated with AH Plus sealer and obturated using gutta-percha. The root canals were sectioned horizontally into coronal, middle, and apical thirds for evaluating the push-out bond strength. A universal testing machine with a compressive loading of 1 mm/min was employed to test the samples. Results: An increased push-out bond strength was noted with GA in coronal one-third compared to EA and SA but not significant compared to MA (P > 0.05). Similar observations were seen in the middle one-third; however, it was statistically significant compared to all other groups (P < 0.05). Also, the difference between the groups in the apical one-third was not significant. SA showed the lowest push-out bond strength than experimental groups, which was significant in all three sections (P < 0.05). Conclusion: The final rinse of 10% gallic acid increased the push-out bond strength of AH Plus to the root dentin in all thirds of the root canal. Hence, gallic acid 10% might be an effective alternative solution in place of synthetic chelators.