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Antibacterial alkaloids from Artabotrys crassifolius Hook.f. & Thomson

Tan KK, Khoo TJ, Rajagopal M, Wiart C

Nat Prod Res, 2015;29(24):2346-9.
PMID: 25738993 DOI: 10.1080/14786419.2015.1013954

Chloroform extract of bark of Artabotrys crassifolius Hook.f. & Thomson exhibited antibacterial activities against both American Type Culture Collection and clinical bacterial strains in vitro with zones of inhibition ranging from 7 to 14 mm. Further analysis of this extract yielded artabotrine, liridine, lysicamine and atherospermidine. Artabotrine displayed a broad array of antibacterial activity mostly against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 1.25 μg/mL to 5 μg/mL. Of note, artabotrine, liridine and lysicamine are bactericidal against Gram-negative extended-spectrum beta-lactamase-producing Klebsiella with MIC values equal 2.5, 2.5 and 10 μg/mL, respectively, and minimum bactericidal concentrations values equal to 2.5, 5 and 20 μg/mL.
Anti-mycobacterial Constituents from Medicinal Plants; A Review

Sarkar N, Dey YN, Kumar D, Rajagopal M

Mini Rev Med Chem, 2021;21(19):3037-3051.
PMID: 34036911 DOI: 10.2174/1389557521666210525120325

Effective treatment of tuberculosis has been hampered by the emergence of drug-resistant strains of Mycobacterium therapeutic facilities tuberculosis. With the global resurgence of tuberculosis with the development of multidrug-resistant cases, there is a call for the development of new drugs to combat these diseases. Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology, and continued to play a significant role in the drug discovery and development process. This review article depicts the various potential plant extracts as well as plant derived phytoconstituents against the H37rv, the most persistent strains of Mycobacterium tuberculosis and its multidrug strains.
Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR)

Jubair N, Rajagopal M, Chinnappan S, Abdullah NB, Fatima A

Evid Based Complement Alternat Med, 2021;2021:3663315.
PMID: 34447454 DOI: 10.1155/2021/3663315

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.
Fulltext Conceptual interpretation and clinical applicability of a systematic review and meta-analysis about prognostic value of apolipoproteins in COVID-19 patients

Rajagopal M, Senthilnathan R, Shetty S, Devi A, Ravishankar Ram M, Samiappan S, et al.

Travel Med Infect Dis, 2022;46:102248.
PMID: 34990864 DOI: 10.1016/j.tmaid.2021.102248
The Potential of Mur Enzymes as Targets for Antimicrobial Drug Discovery

Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.

Curr Drug Targets, 2023;24(8):627-647.
PMID: 37291783 DOI: 10.2174/1389450124666230608150759

The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
Evaluation of phytochemicals and antioxidant potential of a new polyherbal formulation TC-16: additive, synergistic or antagonistic?

Yap VL, Tan LF, Rajagopal M, Wiart C, Selvaraja M, Leong MY, et al.

BMC Complement Med Ther, 2023 Mar 28;23(1):93.
PMID: 36978110 DOI: 10.1186/s12906-023-03921-0

BACKGROUND: Scientific literature has demonstrated the association of free radicals in the aetiology of various chronic diseases. Hence, the identification of potent antioxidants remains a useful task. The combination of multiple herbs in polyherbal formulations (PHF) is often associated with greater therapeutic efficacy due to synergistic interactions. However, antagonism can occur in natural product mixtures and the resultant antioxidant potential might not always be the additive value of the antioxidant properties of each component. In this study, we aimed to evaluate the phytochemicals, antioxidative potential and interaction among the herbs in TC-16, a new PHF comprising Curcuma longa L., Zingiber officinale var. Bentong, Piper nigrum L., Citrofortunella microcarpa (Bunge) Wijnands and Apis dorsata honey.
METHODS: TC-16 was screened for phytochemicals. Phenolic and flavonoid contents of TC-16 and its individual ingredients were determined, followed by assessment of antioxidant properties using in vitro assays including 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) and β-carotene bleaching (BCB) assays. Interactions among the herbs were also investigated by calculating the difference in antioxidant activity and combination index.
RESULTS: Alkaloids, flavonoids, terpenoids, saponins and glycosides were present in TC-16. TC-16 possessed the highest phenolic (46.14 ± 1.40 mg GAE/g) and flavonoid (132.69 ± 1.43 mg CE/g) contents following C. longa. Synergistic antioxidant activity among the herbs was evident in ORAC and BCB assays which uses mainly hydrogen atom transfer-based antioxidant mechanisms.
CONCLUSIONS: TC-16 demonstrated roles in combating free radicals. In a PHF, synergistic interaction among the herbs is observed in some but not all mechanisms. Mechanisms showing synergistic interactions should be highlighted to maximise the beneficial property of the PHF.
Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment

Chandran R, Tohit ERM, Stanslas J, Salim N, Mahmood TMT, Rajagopal M

Semin Thromb Hemost, 2024 Jan 15.
PMID: 38224699 DOI: 10.1055/s-0043-1778103

The management of hemophilia A has undergone a remarkable revolution, in line with technological advancement. In the recent past, the primary concern associated with Factor VIII (FVIII) concentrates was the risk of infections, which is now almost resolved by advanced blood screening and viral inactivation methods. Improving patients' compliance with prophylaxis has become a key focus, as it can lead to improved health outcomes and reduced health care costs in the long term. Recent bioengineering research is directed toward prolonging the recombinant FVIII (rFVIII) coagulant activity and synthesising higher FVIII yields. As an outcome, B-domain deleted, polyethylene glycolated, single-chain, Fc-fused rFVIII, and rFVIIIFc-von Willebrand Factor-XTEN are available for patients. Moreover, emicizumab, a bispecific antibody, is commercially available, whereas fitusiran and tissue factor pathway inhibitor are in clinical trial stages as alternative strategies for patients with inhibitors. With these advancements, noninfectious complications, such as inhibitor development, allergic reactions, and thrombosis, are emerging concerns requiring careful management. In addition, the recent approval of gene therapy is a major milestone toward a permanent cure for hemophilia A. The vast array of treatment options at our disposal today empowers patients and providers alike, to tailor therapeutic regimens to the unique needs of each individual. Despite significant progress in modern treatment options, these highly effective therapies are markedly more expensive than conventional replacement therapy, limiting their access for patients in developing countries.
Fulltext Antibacterial and Antifungal Terpenes from the Medicinal Angiosperms of Asia and the Pacific: Haystacks and Gold Needles

Wiart C, Kathirvalu G, Raju CS, Nissapatorn V, Rahmatullah M, Paul AK, et al.

Molecules, 2023 May 04;28(9).
PMID: 37175283 DOI: 10.3390/molecules28093873

This review identifies terpenes isolated from the medicinal Angiosperms of Asia and the Pacific with antibacterial and/or antifungal activities and analyses their distribution, molecular mass, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and library searches from 1968 to 2022. About 300 antibacterial and/or antifungal terpenes were identified during this period. Terpenes with a MIC ≤ 2 µg/mL are mostly amphiphilic and active against Gram-positive bacteria, with a molecular mass ranging from about 150 to 550 g/mol, and a polar surface area around 20 Å². Carvacrol, celastrol, cuminol, dysoxyhainic acid I, ent-1β,14β-diacetoxy-7α-hydroxykaur-16-en-15-one, ergosterol-5,8-endoperoxide, geranylgeraniol, gossypol, 16α-hydroxy-cleroda-3,13 (14)Z-diene-15,16-olide, 7-hydroxycadalene, 17-hydroxyjolkinolide B, (20R)-3β-hydroxy-24,25,26,27-tetranor-5α cycloartan-23,21-olide, mansonone F, (+)-6,6'-methoxygossypol, polygodial, pristimerin, terpinen-4-ol, and α-terpineol are chemical frameworks that could be candidates for the further development of lead antibacterial or antifungal drugs.
Fulltext Clinical Theragnostic Relationship between Chemotherapeutic Resistance, and Sensitivity and miRNA Expressions in Head and Neck Cancers: A Systematic Review and Meta-Analysis Protocol

Shaw P, Raymond G, Senthilnathan R, Kumarasamy C, Baxi S, Suresh D, et al.

Genes (Basel), 2021 Dec 20;12(12).
PMID: 34946979 DOI: 10.3390/genes12122029

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19-25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient's prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657.
Fulltext Cervical Cancer-Associated Suffering: Estimating the Palliative Care Needs of a Highly Vulnerable Population

Krakauer EL, Kwete X, Kane K, Afshan G, Bazzett-Matabele L, Bien-Aimé DDR, et al.

JCO Glob Oncol, 2021 06;7:862-872.
PMID: 34115522 DOI: 10.1200/GO.21.00025

PURPOSE: To enable design of optimum palliative care for women with cervical cancer, we studied the most common types of suffering and their severity, prevalence, and duration.
METHODS: We first reviewed the literature on the major types, severity, prevalence, and duration of suffering associated with cervical cancer. We then conducted a modified Delphi process with experts in cervical cancer care to supplement the literature. For each type of suffering, we distinguished between decedents (those who die from cervical cancer in a given year) and nondecedents (those who have cervical cancer in a given year but do not die). By applying the suffering prevalence and duration estimates to the number of decedents, nondecedents, and family caregivers in 2017, we were able to estimate their palliative care needs and the intensity of palliative care needed to respond adequately to this suffering.
RESULTS: There is a high prevalence among decedents of moderate or severe pain (84%), vaginal discharge (66%), vaginal bleeding (61%), and loss of faith (31%). Among both decedents and nondecedents, there is a high prevalence of clinically significant anxiety (63% and 50%, respectively), depressed mood (52% and 38%, respectively), and sexual dysfunction (87% and 83%, respectively). Moderate or severe financial distress is prevalent among decedents, nondecedents, and family caregivers (84%, 74%, and 66%, respectively). More than 40% of decedents and nondecedents are abandoned by their intimate partners. Most patients experience some combination of moderate or severe physical, psychological, social, and spiritual suffering. In total, 258,649 decedents and 2,558,857 nondecedents needed palliative care in 2017, approximately 85% of whom were in low- and middle-income countries where palliative care is rarely accessible.
CONCLUSION: Among women with advanced cervical cancer, suffering is highly prevalent and often severe and multifaceted.