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Herbs for Effective Treatment of Diabetes Mellitus Wounds: Medicinal Chemistry and Future Therapeutic Options

Hussan F, Yahaya MF, Teoh SL, Das S

Mini Rev Med Chem, 2018;18(8):697-710.
PMID: 28971772 DOI: 10.2174/1389557517666170927155707

The incidence of diabetes mellitus (DM) has increased globally. Various complications such as blindness, nephropathy leading to renal failure, neuropathy, foot ulceration, amputation, and disturbance in autonomic nervous system were reported. Although, allopathy treatment still remains the treatment of choice, there is a need to look at the easy availability, patient compliance and cheaper cost of the drugs used in day-day practice. In this regard, complementary and alternative medicine has a greater role to play. Numerous plant extracts were shown to exhibit antihyperglycemic properties. In the present review, we surfed published literature in Pubmed and google databases with regard to the herbs used for DM wound treatment. We also discuss the possible mechanism of wound healing in DM with regard to advanced glycation end products, inflammation, macrophages, non-leukocytic cells such as keratinocytes, fibroblasts and endothelial cells, matrix metalloproteinase and miRNA. The review opens the door for effective treatment of DM wounds with plant extracts and plan future treatment options.
Fulltext Role of MicroRNA in Proliferation Phase of Wound Healing

Soliman AM, Das S, Abd Ghafar N, Teoh SL

Front Genet, 2018;9:38.
PMID: 29491883 DOI: 10.3389/fgene.2018.00038

Wound healing is a complex biological process that is generally composed of four phases: hemostasis, inflammation, proliferation, and remodeling. The proliferation phase is crucial for effective healing compared to other phases. Many critical events occur during this phase, i.e., migration of fibroblasts, re-epithelialization, angiogenesis and wound contraction. Chronic wounds are common and are considered a major public health problem. Therefore, there is the increasing need to discover new therapeutic strategies. MicroRNA (miRNA) research in the field of wound healing is in its early phase, but the knowledge of the recent discoveries is essential for developing effective therapies for the treatment of chronic wounds. In this review, we focused on recently discovered miRNAs which are involved in the proliferation phase of wound healing in the past few years and their role in wound healing.
The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish

Mohamad Najib NH, Yahaya MF, Das S, Teoh SL

Int J Neurosci, 2023 Dec;133(8):822-833.
PMID: 34623211 DOI: 10.1080/00207454.2021.1990916

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.
METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.
RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.
CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.
Accessory sulci of the liver. An anatomical study with clinical implications

Othman FB, Latiff AA, Suhaimi FH, Das S

Saudi Med J, 2008 Sep;29(9):1247-9.
PMID: 18813405

To study the presence of accessory sulcus (AS) in the embalmed cadaveric livers, and compare it with the normal liver.
Fulltext The effect of eurycoma longifolia Jack on spermatogenesis in estrogen-treated rats

Wahab NA, Mokhtar NM, Halim WN, Das S

Clinics (Sao Paulo), 2010;65(1):93-8.
PMID: 20126351 DOI: 10.1590/S1807-59322010000100014

There is little data concerning the ability of Eurycoma longifolia Jack (EL) to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats.
Fulltext Fresh soy oil protects against vascular changes in an estrogen-deficient rat model: an electron microscopy study

Adam SK, Das S, Othman F, Jaarin K

Clinics (Sao Paulo), 2009;64(11):1113-9.
PMID: 19936186 DOI: 10.1590/S1807-59322009001100012

To observe the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats.
Chemopreventive efficacy of ginger (Zingiber officinale) in ethionine induced rat hepatocarcinogenesis

Yusof YA, Ahmad N, Das S, Sulaiman S, Murad NA

Afr J Tradit Complement Altern Med, 2008 Oct 25;6(1):87-93.
PMID: 20162046

Ginger (Zingiber officinale Rosco) is widely used in foods as a spice all around the world. It has been reported to have antioxidant and anticarcinogenic properties. We investigated the effect of ginger in ethionine induced rat hepatocarcinogenesis. Male Wistar rats were divided into 5 groups: group 1 and 2 served as controls and they received normal rat chow and olive oil respectively. Group 3 was fed with ginger oleoresin dissolved in olive oil at 100 mg/kg body wt. Group 4 was fed with choline deficient diet and 0.1% ethionine in drinking water (CDE diet), and group 5 received ginger with CDE diet. Blood samples were taken from the orbital sinus at 0 and 8 weeks of experiment for the determination of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and lipid peroxidation end product, malondialdehyde (MDA). Rats were also killed at 8 weeks for the observation of liver tumor formation. CDE diet induced the formation of liver nodules in rats and increased SOD activity. However, it had no effect on catalase, GPx and MDA levels when compared to both controls at 8 weeks of experiment. When CDE rats were treated with ginger, the formation of liver tumour, SOD activity and MDA level reduced, catalase activity was increased but no change was observed for GPx activity when compared to CDE group. In conclusion, ginger supplementation suppressed liver carcinogenesis by scavenging the free radical formation, and by reducing lipid peroxidation.
Fulltext Sleep Related Epilepsy and Pharmacotherapy: An Insight

Kumar J, Solaiman A, Mahakkanukrauh P, Mohamed R, Das S

Front Pharmacol, 2018;9:1088.
PMID: 30319421 DOI: 10.3389/fphar.2018.01088

In the last several decades, sleep-related epilepsy has drawn considerable attention among epileptologists and neuroscientists in the interest of new paradigms of the disease etiology, pathogenesis and management. Sleep-related epilepsy is nocturnal seizures that manifest solely during the sleep state. Sleep comprises two distinct stages i.e., non-rapid eye movement (NREM) and rapid eye movement (REM) that alternate every 90 min with NREM preceding REM. Current findings indicate that the sleep-related epilepsy manifests predominantly during the synchronized stages of sleep; NREM over REM stage. Sleep related hypermotor epilepsy (SHE), benign partial epilepsy with centrotemporal spikes or benign rolandic epilepsy (BECTS), and Panayiotopoulos Syndrome (PS) are three of the most frequently implicated epilepsies occurring during the sleep state. Although some familial types are described, others are seemingly sporadic occurrences. In the present review, we aim to discuss the predominance of sleep-related epilepsy during NREM, established familial links to the pathogenesis of SHE, BECTS and PS, and highlight the present available pharmacotherapy options.
Treatment of dementia with herbs: a short review

Tang CT, Belani LK, Das S, Jaafar MZ

Clin Ter, 2013;164(1):43-6.
PMID: 23455743 DOI: 10.7417/T.2013.1511

Dementia is a common symptom observed in many psychiatric and neurodegenerative diseases. Alzheimer's disease is the most common form of senile dementia seen in the general population. Multiple factors like oxidative stress, apoptosis, mitochondrial dysfunction and inflammation may be related to the neurodegenerative states. Many drugs like cholinesterase have been used for treatment but the progression of the disease still poses a challenge to the clinician. During recent times, herbs have gained much popularity as supplements because of the cost effectiveness, easy availability and fewer side effects. Early diagnosis and proper treatment may help in the prevention of mortality and morbidity concerned with any neurodegenerative disease. Understanding the cellular and molecular biology of the mode of the action of herbal products may be beneficial for researchers and clinicians. The present review article attempts to look into the potential herbal extracts which may act as an antioxidant in combating dementia.
Fulltext Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases

Kumar J, Teoh SL, Das S, Mahakknaukrauh P

Front Physiol, 2017;8:693.
PMID: 28959211 DOI: 10.3389/fphys.2017.00693

Oxidative stress occurs in diabetes, various cancers, liver diseases, stroke, rheumatoid arthritis, chronic inflammation, and other degenerative diseases related to the nervous system. The free radicals have deleterious effect on various organs of the body. This is due to lipid peroxidation and irreversible protein modification that leads to cellular apoptosis or programmed cell death. During recent years, there is a rise in the oral diseases related to oxidative stress. Oxidative stress in oral disease is related to other systemic diseases in the body such as periodontitis, cardiovascular, pancreatic, gastric, and liver diseases. In the present review, we discuss the various pathways that mediate oxidative cellular damage. Numerous pathways mediate oxidative cellular damage and these include caspase pathway, PERK/NRF2 pathway, NADPH oxidase 4 pathways and JNK/mitogen-activated protein (MAP) kinase pathway. We also discuss the role of inflammatory markers, lipid peroxidation, and role of oxygen species linked to oxidative stress. Knowledge of different pathways, role of inflammatory markers, and importance of low-density lipoprotein, fibrinogen, creatinine, nitric oxide, nitrates, and highly sensitive C-reactive proteins may be helpful in understanding the pathogenesis and plan better treatment for oral diseases which involve oxidative stress.
Bedside teaching in undergraduate medical education: issues, strategies, and new models for better preparation of new generation doctors

Salam A, Siraj HH, Mohamad N, Das S, Rabeya Y

Iran J Med Sci, 2011 Mar;36(1):1-6.
PMID: 23365470

Bedside teaching is a vital component of medical education. It is applicable to any situation where teaching is imparted in the presence of patients. In teaching in the patients' presence, learners have the opportunities to use all of their senses and learn the humanistic aspect of medicine such as role modeling, which is vital but difficult to communicate in words. Unfortunately, bedside teaching has been on the decline. To investigate the reasons for the decline in bedside teaching, its importance and its revival, a review of literature was carried out using PubMed and other data bases. The review revealed that the major concerns of bedside teaching were time constraint, false preceptors' concern about patients' comfort, short stay of patients in hospitals, learner distraction by technology, lack of experience and unrealistic faculty expectation. Whatsoever the reasons, bedside teaching cannot be replaced with anything else. There are newer approaches of effective bedside teaching, and the core focus of all such approaches is educational process. A bedside teacher must learn how to involve patients and learners in the educational processes. Moreover, bedside teaching is the process through which learners acquire the skills of communication by asking patients' permission, establishing ground rules, setting time limit, introducing the team, diagnosing learner, diagnosing patient, conducting focused teaching, using simple language, asking patient if there is any question, closing with encouraging thanks, and giving feedback privately. It is most important to ensure a comfortable environment for all participants, the learner, the patient and the bedside teacher. Ongoing faculty development programs on educational processes and realistic faculty expectations may overcome the problems.
Fulltext Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

Thent ZC, Seong Lin T, Das S, Zakaria Z

Evid Based Complement Alternat Med, 2012;2012:628750.
PMID: 23304208 DOI: 10.1155/2012/628750

Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.
Fulltext Use of medicinal plants and natural products for treatment of osteoporosis and its complications

Soelaiman IN, Das S, Shuid AN, Mo H, Mohamed N

Evid Based Complement Alternat Med, 2013;2013:764701.
PMID: 23476703 DOI: 10.1155/2013/764701
Fulltext Extraction of high-molecular-weight DNA from Streptococcus spp. for nanopore sequencing in resource-limited settings

Das S, Delamare-Deboutteville J, Barnes AC, Rudenko O

Microbiologyopen, 2024 Aug;13(4):e1432.
PMID: 39166362 DOI: 10.1002/mbo3.1432

The long-read sequencing platform MinION, developed by Oxford Nanopore Technologies, enables the sequencing of bacterial genomes in resource-limited settings, such as field conditions or low- and middle-income countries. For this purpose, protocols for extracting high-molecular-weight DNA using nonhazardous, inexpensive reagents and equipment are needed, and some methods have been developed for gram-negative bacteria. However, we found that without modification, these protocols are unsuitable for gram-positive Streptococcus spp., a major threat to fish farming and food security in low- and middle-income countries. Multiple approaches were evaluated, and the most effective was an extraction method using lysozyme, sodium dodecyl sulfate, and proteinase K for lysis of bacterial cells and magnetic beads for DNA recovery. We optimized the method to consistently achieve sufficient yields of pure high-molecular-weight DNA with minimal reagents and time and developed a version of the protocol which can be performed without a centrifuge or electrical power. The suitability of the method was verified by MinION sequencing and assembly of 12 genomes of epidemiologically diverse fish-pathogenic Streptococcus iniae and Streptococcus agalactiae isolates. The combination of effective high-molecular-weight DNA extraction and MinION sequencing enabled the discovery of a naturally occurring 15 kb low-copy number mobilizable plasmid in S. iniae, which we name pSI1. We expect that our resource-limited settings-adapted protocol for high-molecular-weight DNA extraction could be implemented successfully for similarly recalcitrant-to-lysis gram-positive bacteria, and it represents a method of choice for MinION-based disease diagnostics in low- and middle-income countries.
Nodular Melanoma Mimicking Keratoacanthoma: Lessons to learn

Muthupalaniappen L, Das S, Md Nor N, Ali SA

Sultan Qaboos Univ Med J, 2012 Aug;12(3):360-3.
PMID: 22912931

A 67-year-old man of Chinese descent presented with a painless nodular lesion that had been present on his right forearm for the previous 3 months. A single, well-defined, dome-shaped, firm nodule with a central keratin plug surrounded by erythema was noted. Keratoacanthoma with secondary bacterial infection was suspected and the patient underwent an excision biopsy. Biopsy of the nodule and immunohistochemical staining supported a diagnosis of nodular malignant melanoma. It should be noted both that nodular malignant melanoma may present with a wide variety of clinical appearances, and that the lack of melanin pigment in nodular malignant melanoma may hinder the diagnosis of this aggressive tumour.
Fulltext Nutrition and physical activity interventions to ameliorate postpartum depression: A scoping review

Yahya NFS, Teng NIMF, Das S, Juliana N

Asia Pac J Clin Nutr, 2021 Dec;30(4):662-674.
PMID: 34967195 DOI: 10.6133/apjcn.202112_30(4).0013

BACKGROUND AND OBJECTIVES: Globally, there is a high prevalence of postpartum depression (17.7%) reported in a recent study among mothers during the postpartum period. It contributes to poor health and well-being among newly delivered women. We reviewed the published effect of nutrition and physical activity interventions on improving and treating postpartum depression.
METHODS AND STUDY DESIGN: The scoping review was performed using Arksey and O'Malley's methodological framework. The systematic search was conducted using Scopus, Pubmed, EBSCOHost and Google Scholar in April 2020, updated in March 2021. Only literature published between January 2010 until February 2021 was searched.
RESULTS: A total of 25 articles were included, of which 23 were randomised controlled trials , and 2 were quasi-experimental studies. Some of studies found improvements in depression (76% out of all studies). On this basis, nutrition or physical activity intervention probably improves postpartum depression. Moreover, the integration of nutrition and physical activity appears to improve depression in the more thorough follow-up of participants . Active involvement of the participant in the interventions was contributory to effectiveness.
CONCLUSIONS: Nutrition and physical activity interventions with appropriate strategy and delivery are promising options for the management of postpartum maternal mental health. More definitive investigation of non-pharmacological interventions to ameliorate depression among postpartum women is warranted.
Fulltext Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction

Kosai NR, Gendeh HS, Norfaezan AR, Razman J, Sutton PA, Das S

Int Surg, 2015 Jun;100(6):1148-52.
PMID: 25578789 DOI: 10.9738/INTSURG-D-14-00205.1

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy.
A review of the use of Piper betel in oxidative stress disorders

Lee CY, Nurul Zaidah AS, Nur Amalina G, Muhammad Azree E, Das S, Zar CT

Clin Ter, 2014;165(5):269-77.
PMID: 25366948 DOI: 10.7417/CT.2014.1758

Increase in prevalence of disease related oxidative stress disorders have been on the rise in the entire world since the past decades. Significant positive effects with few antioxidant properties in the modern drugs pave for the alternative medicines in managing the disease. Piper betel (P. betel), a herb, is known to possess high anti-oxidant, anti-diabetic, anti-atherosclerosis, anti-hyperlipidemic, anti-cancer and neuroprotective property. This review focused on the effect of P. betel on diabetes mellitus, atherosclerosis and chronic kidney disease, Alzheimer's disease and breast cancer. P. betel proved to show positive effects with specific outcomes towards these diseases. Moreover, the promising effect of P. betel in vitro studies was also highlighted in the present review. It is believed that the findings obtained in this review will draw the attention of the medical professionals and general public towards P. betel and it will open the door for further detailed research.
Transarterial angioembolization versus surgery after failed endoscopic therapy for non-variceal upper gastrointestinal bleeding

Jailani RF, Kosai NR, Yaacob NY, Jarmin R, Sutton P, Harunarrashid H, et al.

Clin Ter, 2014;165(6):294-8.
PMID: 25524184 DOI: 10.7417/CT.2014.1771

BACKGROUND AND OBJECTIVE: To compare the outcome of transarterial angioembolization (TAE) and surgery with endoscopically unmanageable non-variceal hemorrhage of the upper gastrointestinal tract.

MATERIALS AND METHODS: A case note review of all patients treated for non-variceal upper gastrointestinal bleeding from January 2006 till January 2012 was performed.

RESULTS: Fifty-four of 667 patients with non-variceal bleeding did not respond to endoscopic treatment. Nine of the 54 patients had incomplete data, leaving 45 patients in the study; 24 had angiography and another 21 had surgery. The two groups were broadly similar in terms of relevant clinical variables. Nineteen of 24 having angiography had embolisation. Re-bleeding recurred in 8 patients (33%) in the TAE group and 6 patients (28.6%) in the surgery group (p = 0.28). There was no statistically significant difference in post procedural complications (81% vs 62.5%, p = 0.17), 30-day mortality (33% vs 29.1%, p = 0.17 ) units of blood transfused (12.24 vs 8.92, p = 0.177) and mean hospital stay (30.7 vs 22.9 days, p = 0.281) observed in patients undergoing surgery as compared to TAE.

CONCLUSIONS: TAE and surgery have similar outcomes in patients with endoscopically unmanageable non-variceal upper gastrointestinal haemorrhage.
Fulltext Engineered silybin nanoparticles educe efficient control in experimental diabetes

Das S, Roy P, Pal R, Auddy RG, Chakraborti AS, Mukherjee A

PLoS One, 2014;9(7):e101818.
PMID: 24991800 DOI: 10.1371/journal.pone.0101818

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17 ± 0.01 µg/lit to 0.57 ± 0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.

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