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Fulltext Medicinal Plants in COVID-19: Potential and Limitations

Lim XY, Teh BP, Tan TYC

Front Pharmacol, 2021;12:611408.
PMID: 33841143 DOI: 10.3389/fphar.2021.611408

Currently, the search to identify treatments and vaccines for novel coronavirus disease (COVID-19) are ongoing. Desperation within the community, especially among the middle-and low-income groups acutely affected by the economic impact of forced lockdowns, has driven increased interest in exploring alternative choices of medicinal plant-based therapeutics. This is evident with the rise in unsubstantiated efficacy claims of these interventions circulating on social media. Based on enquiries received, our team of researchers was given the chance to produce evidence summaries evaluating the potential of complementary interventions in COVID-19 management. Here, we present and discuss the findings of four selected medicinal plants (Nigella sativa, Vernonia amygdalina, Azadirachta indica, Eurycoma longifolia), with reported antiviral, anti-inflammatory, and immunomodulatory effects that might be interesting for further investigation. Our findings showed that only A. indica reported positive antiviral evidence specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on preliminary in silico data while all four medicinal plants demonstrated differential anti-inflammatory or immunomodulatory effects. The definitive roles of these medicinal plants in cytokine storms and post-infection complications remains to be further investigated. Quality control and standardisation of medicinal plant-based products also needs to be emphasized. However, given the unprecedented challenges faced, ethnopharmacological research should be given a fair amount of consideration for contribution in this pandemic.
Eight-and-a-half syndrome as the first presentation of multiple sclerosis in an Asian male: a case report

Lim XY, Wai YZ, Yong YX, Lim LT

J Med Case Rep, 2023 Mar 06;17(1):99.
PMID: 36879252 DOI: 10.1186/s13256-022-03699-8

BACKGROUND: Multiple sclerosis is a diffuse chronic demyelinating disease of the central nervous system. It is relatively uncommon in the Asian population and even more so in males. Despite the usual involvement of the brainstem, eight-and-a-half syndrome remains a rare first presentation in multiple sclerosis. Only a few cases have been reported previously, but none involving the Asian population. Eight-and-a-half syndrome, a neuro-ophthalmological condition, is characterized by one-and-a-half syndrome with ipsilateral lower facial nerve palsy, which localizes lesions to the pontine tegmentum. This case report demonstrates the first case of eight-and-a-half syndrome as the first presentation of multiple sclerosis in an Asian male.
CASE PRESENTATION: A healthy 23-year-old Asian man presented with sudden onset of diplopia followed by left-sided facial asymmetry for 3 days. Assessment of extraocular movement revealed left conjugate horizontal gaze palsy. On right gaze, there was limited left eye adduction and horizontal nystagmus of the right eye. These findings were consistent with a left-sided one-and-a-half syndrome. Prism cover test revealed left esotropia of 30 prism diopters. Cranial nerve examination showed left lower motor neuron facial nerve palsy, while other neurological examination was normal. Magnetic resonance imaging brain showed multifocal T2 fluid attenuated inversion recovery hyperintense lesions, involving bilateral periventricular, juxtacortical, and infratentorial regions. A focal gadolinium contrast-enhanced lesion with open ring sign on T1 sequence was seen at the left frontal juxtacortical region. Multiple sclerosis was diagnosed on the basis of the clinical and radiological evidence, which fulfilled the 2017 McDonald criteria. Positive oligoclonal bands in cerebrospinal fluid analysis further confirmed our diagnosis. He had a complete resolution of symptoms 1 month after a course of pulsed corticosteroid therapy, and was subsequently placed on maintenance therapy with interferon beta-1a.
CONCLUSION: This case illustrates eight-and-a-half syndrome as the first presentation of a diffuse central nervous system pathology. A wide range of differential diagnoses needs to be considered in such a presentation as based on the patient's demographics and risk factors.
Acupuncture for the reduction of post-operative pain in a patient with symptomatic irreversible pulpitis: a case report

Sng KS, Sin YS, Bhatia S, Kohli S, Lim XY, Ong JY

Acupunct Med, 2022 Jan 12.
PMID: 35018808 DOI: 10.1177/09645284211073336
A Systematic Review and Meta-Analysis on the Therapeutic Efficacy of Heparin and Low Molecular Weight Heparins in Animal Studies of Traumatic Brain Injury

Aiyede M, Lim XY, Russell AAM, Patel RP, Gueven N, Howells DW, et al.

J Neurotrauma, 2023 Jan;40(1-2):4-21.
PMID: 35880422 DOI: 10.1089/neu.2022.0020

The identification of effective pharmacotherapies for traumatic brain injury (TBI) remains a major challenge. Treatment with heparin and its derivatives is associated with neuroprotective effects after experimental TBI; however, the optimal dosage and method of administration, modes of action, and effects on hemorrhage remain unclear. Therefore, this review aimed to systematically evaluate, analyze, and summarize the available literature on the use of heparin and low molecular weight heparins (LMWHs) as treatment options for experimental TBI. We searched two online databases (PubMed and ISI Web of Science) to identify relevant studies. Data pertaining to TBI paradigm, animal subjects, drug administration, and all pathological and behavior outcomes were extracted. Eleven studies met our pre-specified inclusion criteria, and for outcomes with sufficient numbers, data from seven publications were analyzed in a weighted mean difference meta-analysis using a random-effects model. Study quality and risk of bias were also determined. Meta-analysis revealed that heparin and its derivatives decreased brain edema, leukocyte rolling, and vascular permeability, and improved neurological function. Further, treatment did not aggravate hemorrhage. These findings must be interpreted with caution, however, because they were determined from a limited number of studies with substantial heterogeneity. Also, overall study quality was low based on absences of data reporting, and potential publication bias was identified. Importantly, we found that there are insufficient data to evaluate the variables we had hoped to investigate. The beneficial effects of heparin and LMWHs, however, suggest that further pre-clinical studies are warranted.
Fulltext Carica papaya L. Leaf: A Systematic Scoping Review on Biological Safety and Herb-Drug Interactions

Lim XY, Chan JSW, Japri N, Lee JC, Tan TYC

Evid Based Complement Alternat Med, 2021;2021:5511221.
PMID: 34040647 DOI: 10.1155/2021/5511221

INTRODUCTION: The Carica papaya L. leaf is gaining interest as a potential therapeutic agent for alleviating dengue- and non-dengue-associated thrombocytopaenia. In that regard, safety considerations are as important as efficacy potential. The safety evaluation of botanical products for human use is complicated by variable formulations, complex phytochemical composition, and extrinsic toxicants. This review aimed to systematically collate related safety clinical and preclinical data, as well as reports on herb-drug interactions of C. papaya leaf consumption.
METHODS: A systematic search using predetermined keywords on electronic databases (MEDLINE, Cochrane Library Central, LILACS, and Web of Science) and grey literature was conducted. Relevant clinical and preclinical studies were identified, screened, and analysed to present an overall safety profile of C. papaya leaf consumption.
RESULTS: A total of 41 articles were included (23 clinical, 5 ongoing trials, and 13 preclinical) for descriptive analysis on study characteristics, adverse reactions, toxicity findings, and herb-drug interactions, from which 13 randomised controlled and quasiexperimental trials were further assessed for risk of bias and reporting quality. Overall, C. papaya leaf consumption (in the form of juice and standardised aqueous extract) was well tolerated by adult humans for short durations (
Fulltext Zingiber zerumbet: A Scoping Review of its Medicinal Properties

Chan JSW, Lim XY, Japri N, Ahmad IF, Tan TYC

Planta Med, 2024 Mar;90(3):204-218.
PMID: 38035621 DOI: 10.1055/a-2219-9801

Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.
Fulltext The Health Effects of Chocolate and Cocoa: A Systematic Review

Tan TYC, Lim XY, Yeo JHH, Lee SWH, Lai NM

Nutrients, 2021 Aug 24;13(9).
PMID: 34578786 DOI: 10.3390/nu13092909

Chocolate has a history of human consumption tracing back to 400 AD and is rich in polyphenols such as catechins, anthocyanidins, and pro anthocyanidins. As chocolate and cocoa product consumption, along with interest in them as functional foods, increases worldwide, there is a need to systematically and critically appraise the available clinical evidence on their health effects. A systematic search was conducted on electronic databases such as MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) using a search strategy and keywords. Among the many health effects assessed on several outcomes (including skin, cardiovascular, anthropometric, cognitive, and quality of life), we found that compared to controls, chocolate or cocoa product consumption significantly improved lipid profiles (triglycerides), while the effects of chocolate on all other outcome parameters were not significantly different. In conclusion, low-to-moderate-quality evidence with short duration of research (majority 4-6 weeks) showed no significant difference between the effects of chocolate and control groups on parameters related to skin, blood pressure, lipid profile, cognitive function, anthropometry, blood glucose, and quality of life regardless of form, dose, and duration among healthy individuals. It was generally well accepted by study subjects, with gastrointestinal disturbances and unpalatability being the most reported concerns.
Fulltext Efficacy and Safety of Morinda citrifolia L. (Noni) as a Potential Anticancer Agent

Chanthira Kumar H, Lim XY, Mohkiar FH, Suhaimi SN, Mohammad Shafie N, Chin Tan TY

Integr Cancer Ther, 2022;21:15347354221132848.
PMID: 36448674 DOI: 10.1177/15347354221132848

Cancer is a major cause of morbidity and mortality worldwide and therefore there has been interest in discovering the phytoconstituents of medicinal plants exhibiting anticancer activities. Morinda citrifolia L., commonly known as Noni, has shown anticancer properties in in vitro, in vivo, and in clinical studies. A systematic review was conducted to collate scientific evidence on the anticancer properties of M. citrifolia using pre-determined keywords on 5 electronic databases: MEDLINE, CENTRAL, LILACS, Web of Science, and EBSCOHost. A total of 51 clinical and preclinical studies comprising 41 efficacy and 10 safety studies were included in this review. Our findings showed that M. citrifolia demonstrated various anticancer properties in different cancer models, via multiple mechanisms including antitumor, antiproliferative, pro-apoptotic, antiangiogenesis, antimigratory, anti-inflammatory, and immunomodulatory activities. M. citrifolia is deemed to be a potentially valuable medicinal plant in the treatment of cancer through its many intrinsic pathways. More well-designed and reported preclinical efficacy and safety studies are needed to allow for better translation into future clinical studies which could further substantiate the role of M. citriflolia in cancer treatment.
Fulltext Structured Manual Muscle Testing of the Lower Limbs

Lim XY, Wong JKC, Idris Z, Ghani ARI, Abdul Halim S, Abdullah JM

Malays J Med Sci, 2023 Oct;30(5):206-220.
PMID: 37928783 DOI: 10.21315/mjms2023.30.5.17

An accurate and reliable neurological examination is pivotal in diagnosing patients with neurological and neurosurgical conditions. Despite the advancement of neuroscientific knowledge and the ever-progressing technologies and modalities that are being adopted to help achieve the challenge of accurate diagnosis, the neurologic examination is still crucial in both ambulatory and emergency settings. It provides the physician a tool to recognise neurologic involvement in certain disease states, and thereby allow proper work-up and treatment for patients. A basic neurologic examination can be performed rapidly with practice. Manual muscle testing of the lower limbs was carried out in accordance with a bedside clinical examination involving a clinical personnel examiner and a patient. This testing was performed in a rostro-caudal manner, starting from the hip and progressing to the toes. The neurological exam can be intimidating to perform for a lot of physicians. Deficiencies in accurate muscle testing have always presented a challenge for medical students and clinicians. By referring to the examination methods mentioned in our text and with the help of related video, it is our aim to improve the quality of neurological examination among medical personnel so that diseases may be recognised and managed earlier in their course.
Fulltext Cannabis sativa subsp. sativa's pharmacological properties and health effects: A scoping review of current evidence

Lim XY, Tan TYC, Muhd Rosli SH, Sa'at MNF, Sirdar Ali S, Syed Mohamed AF

PLoS One, 2021;16(1):e0245471.
PMID: 33465140 DOI: 10.1371/journal.pone.0245471

INTRODUCTION: Hemp (Cannabis sativa subsp. sativa), commonly used for industrial purposes, is now being consumed by the public for various health promoting effects. As popularity of hemp research and claims of beneficial effects rises, a systematic collection of current scientific evidence on hemp's health effects and pharmacological properties is needed to guide future research, clinical, and policy decision making.
OBJECTIVE: To provide an overview and identify the present landscape of hemp research topics, trends, and gaps.
METHODS: A systematic search and analysis strategy according to the preferred reporting items for systematic review and meta-analysis-ScR (PRISMA-ScR) checklist on electronic databases including MEDLINE, OVID (OVFT, APC Journal Club, EBM Reviews), Cochrane Library Central and Clinicaltrials.gov was conducted to include and analyse hemp research articles from 2009 to 2019.
RESULTS: 65 primary articles (18 clinical, 47 pre-clinical) were reviewed. Several randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) improving spontaneous bowel movement in functional constipation. There was also evidence suggesting benefits in cannabis dependence, epilepsy, and anxiety disorders. Pre-clinically, hemp derivatives showed potential anti-oxidative, anti-hypertensive, anti-inflammatory, anti-diabetic, anti-neuroinflammatory, anti-arthritic, anti-acne, and anti-microbial activities. Renal protective effects and estrogenic properties were also exhibited in vitro.
CONCLUSION: Current evidence on hemp-specific interventions are still preliminary, with limited high quality clinical evidence for any specific therapeutic indication. This is mainly due to the wide variation in test item formulation, as the multiple variants of this plant differ in their phytochemical and bioactive compounds. Future empirical research should focus on standardising the hemp plant for pharmaceutical use, and uniformity in experimental designs to strengthen the premise of using hemp in medicine.
Fulltext Neurological Applications of Celery (Apium graveolens): A Scoping Review

Tan TYC, Lim XY, Norahmad NA, Chanthira Kumar H, Teh BP, Lai NM, et al.

Molecules, 2023 Aug 02;28(15).
PMID: 37570794 DOI: 10.3390/molecules28155824

Apium graveolens is an indigenous plant in the family Apiaceae, or Umbelliferae, that contains many active compounds. It has been used traditionally to treat arthritic conditions, gout, and urinary infections. The authors conducted a scoping review to assess the quality of available evidence on the overall effects of celery when treating neurological disorders. A systematic search was performed using predetermined keywords in selected electronic databases. The 26 articles included upon screening consisted of 19 in vivo studies, 1 published clinical trial, 4 in vitro studies and 2 studies comprising both in vivo and in vitro methods. A. graveolens and its bioactive phytoconstituent, 3-n-butylphthalide (NBP), have demonstrated their effect on neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke-related neurological complications, depression, diabetes-related neurological complications, and epilepsy. The safety findings were minimal, showing that NBP is safe for up to 18 weeks at 15 mg/kg in animal studies, while there were adverse effects (7%) reported when consuming NBP for 24 weeks at 600 mg daily in human trials. In conclusion, the safety of A. graveolens extract and NBP can be further investigated clinically on different neurological disorders based on their potential role in different targeted pathways.
Fulltext Medicinal plants for allergic rhinitis: A systematic review and meta-analysis

Lim XY, Lau MS, Zolkifli NA, Sastu Zakaria UR, Mohd Rahim NS, Lai NM, et al.

PLoS One, 2024;19(4):e0297839.
PMID: 38603736 DOI: 10.1371/journal.pone.0297839

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.
Microwave pyrolysis with KOH/NaOH mixture activation: A new approach to produce micro-mesoporous activated carbon for textile dye adsorption

Liew RK, Azwar E, Yek PNY, Lim XY, Cheng CK, Ng JH, et al.

Bioresour Technol, 2018 Oct;266:1-10.
PMID: 29936405 DOI: 10.1016/j.biortech.2018.06.051

A micro-mesoporous activated carbon (AC) was produced via an innovative approach combining microwave pyrolysis and chemical activation using NaOH/KOH mixture. The pyrolysis was examined over different chemical impregnation ratio, microwave power, microwave irradiation time and types of activating agents for the yield, chemical composition, and porous characteristic of the AC obtained. The AC was then tested for its feasibility as textile dye adsorbent. About 29 wt% yield of AC was obtained from the banana peel with low ash and moisture (<5 wt%), and showed a micro-mesoporous structure with high BET surface area (≤1038 m2/g) and pore volume (≤0.80 cm3/g), indicating that it can be utilized as adsorbent to remove dye. Up to 90% adsorption of malachite green dye was achieved by the AC. Our results indicate that the microwave-activation approach represents a promising attempt to produce good quality AC for dye adsorption.
Inapparent dengue in a community living among dengue-positive Aedes mosquitoes and in a hospital in Klang Valley, Malaysia

Tan W, Liew JWK, Selvarajoo S, Lim XY, Foo CJ, Refai WF, et al.

Acta Trop, 2020 Apr;204:105330.
PMID: 31917959 DOI: 10.1016/j.actatropica.2020.105330

The public health burden of dengue is most likely under reported. Current dengue control measures only considered symptomatic dengue transmission. Hence, there is a paucity of information on the epidemiology of inapparent dengue. This study reports that many people have been unknowingly exposed to dengue infection. Almost 10% and 70% of individuals without any history of dengue infection and living in a dengue hotspot, in Selangor, Malaysia, were dengue IgM and IgG positive respectively. When dengue-positive mosquitoes were detected in the hotspot, 11 (6.3%) of the 174 individuals tested were found to have dengue viremia, of which 10 were asymptomatic. Besides, upon detection of a dengue-infected mosquito, transmission was already widespread. In a clinical setting, it appears that people living with dengue patients have been exposed to dengue, whether asymptomatic or symptomatic. They can either have circulating viral RNA and/or presence of NS1 antigen. It is also possible that they are dengue seropositive. Collectively, the results indicate that actions taken to control dengue transmission after the first report of dengue cases may be already too late. The current study also revealed challenges in diagnosing clinically inapparent dengue in hyperendemic settings. There is no one best method for diagnosing inapparent dengue. This study demonstrates empirical evidence of inapparent dengue in different settings. Early dengue surveillance in the mosquito population and active serological/virological surveillance in humans can go hand in hand. More studies are required to investigate the epidemiology, seroprevalence, diagnostics, and control of inapparent dengue. It is also crucial to educate the public, health staff and medical professionals on asymptomatic dengue and to propagate awareness, which is important for controlling transmission.
Fulltext Knowledge, attitude and practice on dengue prevention and dengue seroprevalence in a dengue hotspot in Malaysia: A cross-sectional study

Selvarajoo S, Liew JWK, Tan W, Lim XY, Refai WF, Zaki RA, et al.

Sci Rep, 2020 Jun 12;10(1):9534.
PMID: 32533017 DOI: 10.1038/s41598-020-66212-5

Dengue has become a global public health problem. Despite reactive efforts by the government in Malaysia, the dengue cases are on the increase. Adequate knowledge, positive attitude and correct practice for dengue control are essential to stamp out the disease. Hence, this study aims to assess the factors associated with dengue knowledge, attitude and practice (KAP), as well as the association with dengue IgM and IgG seropositivity. A community-based cross-sectional study was conducted in a closed, dengue endemic area with multi-storey dwellings . Five hundred individuals (aged 18 years and above) were approached for pre-tested KAP and seroprevalences assessment. The study showed only half of the total participants have good knowledge (50.7%) but they had insufficient knowledge about dengue during pregnancy. 53.2% of people had poor attitude and 50.2% reported poor practice for dengue control. Out of 85 respondents who agreed to participate in the dengue seroprevalence study, 74.1% (n = 63) were positive for dengue IgG and 7.1% (n = 6) were positive for dengue IgM. Among all sociodemographic variable, race is the only independent predicator for all KAP levels (P
Antimicrobial and Antiproliferative Effects of Zingiberaceae Oils: A Natural Solution for Oral Health

Amil MA, Rahman SNSA, Yap LF, Razak FA, Bakri MM, Salem LSO, et al.

Chem Biodivers, 2024 Mar;21(3):e202301836.
PMID: 38253795 DOI: 10.1002/cbdv.202301836

Essential oils have been recognised for their potential benefits in oral care. The aim of this study was to evaluate the antibacterial and antiproliferative activity of essential oils derived from four Zingiberaceae species. A combination of GC/MS and GC-FID was employed to analyse these essential oils. The results showed that β-myrcene (79.77 %) followed by ethyl-cinnamate (40.14 %), β-curcumene (34.90 %), and alloaromadendrene (25.15 %) as the primary constituents of Curcuma mangga, Curcuma xanthorrhiza, Kaempferia galanga and Curcuma aeruginosa, respectively. The Zingiberaceae oils were tested for their antibacterial activity against oral bacteria using the disc diffusion test. Curcuma xanthorrhiza oil showed the largest inhibition zones against Streptococcus mitis (19.50±2.22 mm) and Streptococcus sanguinis (15.04±3.05 mm). Similarly, Curcuma mangga oil exhibited significant antibacterial activity against Streptococcus mutans (12.55±0.45 mm) and mixed oral bacteria (15.03±3.82 mm). Furthermore, the MTT viability assay revealed moderate inhibitory activity of these essential oils against H103 and ORL-204 oral cancer cells. The study findings demonstrate that Curcuma xanthorrhiza and Curcuma mangga essential oils have potent antibacterial properties, suggesting their potential use as natural alternatives to synthetic antibacterial agents in oral care products. However, further investigations are necessary to fully explore their therapeutic applications.

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