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Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies

Thu HE, Mohamed IN, Hussain Z, Jayusman PA, Shuid AN

Chin J Nat Med, 2017 Jan;15(1):71-80.
PMID: 28259255 DOI: 10.1016/S1875-5364(17)30010-9

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.
Fulltext Wound Healing Properties of Selected Natural Products

Ibrahim N', Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S, et al.

Int J Environ Res Public Health, 2018 10 25;15(11).
PMID: 30366427 DOI: 10.3390/ijerph15112360

Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.
Fulltext Health-Seeking Behavior for Erectile Dysfunction in Methadone Maintenance Treatment Patients

Ramli FF, Shuid AN, Pakri Mohamed RM, Tg Abu Bakar Sidik TMI, Naina Mohamed I

Int J Environ Res Public Health, 2019 11 01;16(21).
PMID: 31683816 DOI: 10.3390/ijerph16214249

Background: Erectile dysfunction (ED) is commonly associated with methadone usage. However, little data is known regarding the health-seeking behavior for ED in the methadone maintenance treatment (MMT) population. This study aimed to determine the health-seeking behavior of MMT patients with ED who perceived themselves as having ED. We aimed to assess the attitudes and health-seeking behavior, the effectiveness of the treatment and the factors associated with treatment-seeking behavior. Methods: This was an observational questionnaire-based study. Patients were first screened for ED (n = 154) using the International Index of Erectile Function-5 (IIEF-5). Fifty patients with ED were evaluated for health-seeking behavior for ED. Results: More than half of the patients who thought they had ED (78%) believed their sex life was affected. Most patients (48%) did not seek any information regarding ED. Education level (p = 0.017) and marital status (p = 0.008) were predictive factors of health-seeking behavior. Conclusions: The health-seeking rate among MMT patients with ED needs to be improved. Measures to increase awareness of ED in MMT patients should be taken to overcome the barrier to health-seeking behavior. Health practitioners should take action to screen ED in this population to increase the detection rate and offer appropriate management according to the patients' needs.
Fulltext Combined virgin coconut oil and tocotrienol-rich fraction protects against bone loss in osteoporotic rat model

Malik MMA, Othman F, Hussan F, Shuid AN, Saad QM

Vet World, 2019 Dec;12(12):2052-2060.
PMID: 32095059 DOI: 10.14202/vetworld.2019.2052-2060

Background and Aim: Both virgin coconut oil (VCO) and tocotrienol-rich fraction (TRF) are rich in antioxidants and may protect the bone against bone loss induced by ovariectomy and high-fat diet. The study aimed to determine the protective effects of combined therapy of VCO and TRF on osteoporosis in ovariectomized (OVX) rat fed with high-fat diet.
Materials and Methods: Thirty-six female Sprague-Dawley rats were divided into six groups: Sham-operated (SHAM), OVX control, OVX and given Premarin at 64.5 µg/kg (OVX+E2), OVX and given VCO at 4.29 ml/kg (OVX+V), OVX and given TRF at 30 mg/kg (OVX+T), and OVX and given a combination of VCO at 4.29 ml/kg and TRF at 30 mg/kg (OVX+VT). Following 24 weeks of treatments, blood and femora samples were taken for analyses.
Results: There were no significant differences in serum osteocalcin levels between the groups (p>0.05), while serum C-terminal telopeptide of Type I collagen levels of the OVX+VT group were significantly lower than the other groups (p<0.05). The dynamic bone histomorphometry analysis of the femur showed that the double-labeled surface/bone surface (dLS/BS), mineral apposition rate, and bone formation rate/BS of the OVX+E2, OVX+T, and OVX+VT groups were significantly higher than the rest of the groups (p<0.05).
Conclusion: A combination of VCO and TRF has the potential as a therapeutic agent to restore bone loss induced by ovariectomy and high-fat diet.
Fulltext The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence

Wong SK, Mohamad NV, Ibrahim N', Chin KY, Shuid AN, Ima-Nirwana S

Int J Mol Sci, 2019 Mar 22;20(6).
PMID: 30909398 DOI: 10.3390/ijms20061453

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.
Fulltext Lifestyle indices of body composition and obesity risk and prevalence among multi-ethnic adolescents in Malaysia

Zulfarina MS, Sharif R, Mokhtar SA, Shuid AN, Naina-Mohamed I

Front Pediatr, 2022;10:899014.
PMID: 36389377 DOI: 10.3389/fped.2022.899014

The prevalence of childhood obesity in Malaysia has doubled in less than a decade. Moreover, being overweight and obese have been associated with immediate and later comorbidities, thus emphasizing the need to prevent obesity from an early age. This cross-sectional study involved 923 multi-ethnic Malaysian adolescents aged between 15 and 17 years old. Body composition was estimated using bioelectrical impedance analysis. Body mass index (BMI) classification was based on the World Health Organization (WHO) growth reference and the International Obesity Task Force (IOTF) cut-off. Meanwhile, the Child Growth Foundation (CGF) body fat reference was used to classify adolescents' adiposity. Lifestyle indices including physical activity, sedentary behavior, supplement intake, smoking and alcohol status were assessed via questionnaires. A high prevalence of overweight/obesity among the adolescents was observed according to the CGF (26%), followed by that of the WHO (24%) and then the IOTF (23%) cut-off, with high concordance values between each pair. After adjustment, a significant association was found between physical activity (PAQ score) and lean mass (p = 0.027). No lifestyle determinant was found to be a significant predictor of fat percentage. A high sedentary level increased the likelihood of obesity (OR 3.0, p
The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism

Hairi HA, Shuid AN, Ibrahim N', Jamal JA, Mohamed N, Mohamed IN

Curr Drug Targets, 2019;20(2):192-200.
PMID: 28814228 DOI: 10.2174/1389450118666170816123740

BACKGROUND: Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause.
OBJECTIVE: Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition.
RESULTS: The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review.
CONCLUSION: The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.
The use of selective estrogen receptor modulators on bone health in men

Wong SK, Mohamad NV, Jayusman PA, Shuid AN, Ima-Nirwana S, Chin KY

Aging Male, 2019 Jun;22(2):89-101.
PMID: 29508640 DOI: 10.1080/13685538.2018.1448058

Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.
Quality of energy intake in Malaysian adolescents: prevalence, characteristics, determinants and impact of implausible reporters

Zulfarina MS, Sharif R, Sharkawi AM, Mokhtar SA, Shuid AN, Naina-Mohamed I

Public Health Nutr, 2023 Jan;26(1):122-131.
PMID: 35321764 DOI: 10.1017/S1368980022000726

OBJECTIVE: Misreporting of energy intake (EI) in nutritional epidemiology is common and even severe among adolescents. Thus, the current study aims to examine the presence, bias and impact introduced by implausible reporters.
DESIGN: Cross-sectional.
SETTING: Central and eastern regions of Peninsular Malaysia.
PARTICIPANTS: A stratified random sampling was employed to select 917 secondary school-going adolescents (aged 15-17 years).
RESULTS: The prevalence of under-reporters was 17·4 %, while no over-reporters were identified. Under-reporters had higher body composition and lower dietary intakes (except for vitamin C, Cr and Fl) compared with plausible reporters (P < 0·05). Adolescents with overweight and obesity had a higher odds of under-reporting compared with under-/normal weight adolescents (P < 0·001). In model 3, the highest regression coefficient (R2 = 0·404, P < 0·001) was obtained after adjusting for reporting status.
CONCLUSIONS: Overweight and obese adolescents were more likely to under-report their food intake and consequently affect nutrient intakes estimates. Future analyses that include nutrient intake data should adjust for reporting status so that the impact of misreporting on study outcomes can be conceded and consequently improve the accuracy of dietary-related results.
Fulltext Overview on postmenopausal osteoporosis and periodontitis: The therapeutic potential of phytoestrogens against alveolar bone loss

Jayusman PA, Nasruddin NS, Baharin B, Ibrahim N', Ahmad Hairi H, Shuid AN

Front Pharmacol, 2023;14:1120457.
PMID: 36909165 DOI: 10.3389/fphar.2023.1120457

Osteoporosis and periodontitis are two major chronic diseases of postmenopausal women. The association between these two diseases are evident through systemic bone loss and alveolar bone loss. Both postmenopausal osteoporosis and periodontitis impose a considerable personal and socioeconomic burden. Biphosphonate and hormone replacement therapy are effective in preventing bone loss in postmenopausal osteoporosis and periodontitis, but they are coupled with severe adverse effects. Phytoestrogens are plant-based estrogen-like compounds, which have been used for the treatment of menopause-related symptoms. In the last decades, numerous preclinical and clinical studies have been carried out to evaluate the therapeutic effects of phytoestrogens including bone health. The aim of this article is to give an overview of the bidirectional interrelationship between postmenopausal osteoporosis and periodontitis, summarize the skeletal effects of phytoestrogens and report the most studied phytoestrogens with promising alveolar bone protective effect in postmenopausal osteoporosis model, with and without experimental periodontitis. To date, there are limited studies on the effects of phytoestrogens on alveolar bone in postmenopausal osteoporosis. Phytoestrogens may have exerted their bone protective effect by inhibiting bone resorption and enhancing bone formation. With the reported findings on the protective effects of phytoestrogens on bone, well-designed trials are needed to better investigate their therapeutic effects. The compilation of outcomes presented in this review may provide an overview of the recent research findings in this field and direct further in vivo and clinical studies in the future.
Fulltext Association between Viral Infections and Risk of Autistic Disorder: An Overview

Shuid AN, Jayusman PA, Shuid N, Ismail J, Kamal Nor N, Mohamed IN

Int J Environ Res Public Health, 2021 Mar 10;18(6).
PMID: 33802042 DOI: 10.3390/ijerph18062817

Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included "rubella and autism", "cytomegalovirus and autism", "influenza virus and autism", "Zika virus and autism", "COVID-19 and autism". Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.
Fulltext Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

Fathilah SN, Mohamed N, Muhammad N, Mohamed IN, Soelaiman IN, Shuid AN

BMC Complement Altern Med, 2013 Sep 05;13:217.
PMID: 24007208 DOI: 10.1186/1472-6882-13-217

BACKGROUND: Labisia Pumila var. alata (LPva) has shown potential as an alternative to estrogen replacement therapy (ERT) in prevention of estrogen-deficient osteoporosis. In earlier studies using postmenopausal model, LPva was able to reverse the ovariectomy-induced changes in biochemical markers, bone calcium, bone histomorphometric parameters and biomechanical strength. The mechanism behind these protective effects is unclear but LPva may have regulated factors that regulate bone remodeling. The aim of this study is to determine the bone-protective mechanism of LPva by measuring the expressions of several factors involved in bone formative and resorptive activities namely Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), Macrophage-Colony Stimulating Factor (MCSF) and Bone Morphogenetic Protein-2 (BMP-2).
METHODS: Thirty-two female Wistar rats were randomly divided into four groups: Sham-operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LPva) and ovariectomized with ERT (Premarin) (ERT). The LPva and ERT were administered via daily oral gavages at doses of 17.5 mg/kg and 64.5 μg/kg, respectively. Following two months of treatment, the rats were euthanized and the gene expressions of BMP-2, OPG, RANKL and MCSF in the femoral bones were measured using a branch - DNA technique.
RESULTS: The RANKL gene expression was increased while the OPG and BMP-2 gene expressions were reduced in the OVXC group compared to the SHAM group. There were no significant changes in the MCSF gene expressions among the groups. Treatment with either LPva or ERT was able to prevent these ovariectomy-induced changes in the gene expressions in ovariectomized rats with similar efficacy.
CONCLUSION: LPva may protect bone against estrogen deficiency-induced changes by regulating the RANKL, OPG and BMP-2 gene expressions.
Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

Estai MA, Suhaimi F, Das S, Shuid AN, Mohamed Z, Soelaiman IN

Clinics (Sao Paulo), 2011;66(12):2113-9.
PMID: 22189738

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-b) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats.
METHODS: Thirty female Sprague-Dawley rats weighing 200-250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 mg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing.
RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02).
CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.
Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

Estai MA, Suhaimi FH, Das S, Fadzilah FM, Alhabshi SM, Shuid AN, et al.

Clinics (Sao Paulo), 2011;66(5):865-72.
PMID: 21789393

INTRODUCTION: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties.
OBJECTIVES: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state.
METHODS: A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment.
RESULTS: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 ± 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 ± 4.05, 22.4 ± 4.14 and 17.5 ± 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05).
CONCLUSION: The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.
Protective effects of Tualang honey on bone structure in experimental postmenopausal rats

Zaid SS, Sulaiman SA, Othman NH, Soelaiman IN, Shuid AN, Mohamad N, et al.

Clinics (Sao Paulo), 2012 Jul;67(7):779-84.
PMID: 22892923

OBJECTIVE: The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats.
METHODS: Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment.
RESULTS: All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group.
CONCLUSION: In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.
Fulltext Recent Advances in Nanoencapsulation Systems Using PLGA of Bioactive Phenolics for Protection against Chronic Diseases

Abdul Rahim R, Jayusman PA, Muhammad N, Ahmad F, Mokhtar N, Naina Mohamed I, et al.

Int J Environ Res Public Health, 2019 Dec 06;16(24).
PMID: 31817699 DOI: 10.3390/ijerph16244962

Plant-derived polyphenolic compounds have gained widespread recognition as remarkable nutraceuticals for the prevention and treatment of various disorders, such as cardiovascular, neurodegenerative, diabetes, osteoporosis, and neoplastic diseases. Evidence from the epidemiological studies has suggested the association between long-term consumption of diets rich in polyphenols and protection against chronic diseases. Nevertheless, the applications of these phytochemicals are limited due to its low solubility, low bioavailability, instability, and degradability by in vivo and in vitro conditions. Therefore, in recent years, newer approaches have been attempted to solve the restrictions related to their delivery system. Nanoencapsulation of phenolic compounds with biopolymeric nanoparticles could be a promising strategy for protection and effective delivery of phenolics. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers that has attracted considerable attention due to its attractive properties. In this review, our main goal is to cover the relevant recent studies that explore the pharmaceutical significance and therapeutic superiority of the advance delivery systems of phenolic compounds using PLGA-based nanoparticles. A summary of the recent studies implementing encapsulation techniques applied to polyphenolic compounds from plants confirmed that nanoencapsulation with PLGA nanoparticles is a promising approach to potentialize their therapeutic activity.
Fulltext Histological changes in the fracture callus following the administration of water extract of piper sarmentosum (daun kadok) in estrogen-deficient rats

Estai MA, Soelaiman IN, Shuid AN, Das S, Ali AM, Suhaimi FH

Iran J Med Sci, 2011 Dec;36(4):281-8.
PMID: 23115413

BACKGROUND: The fracture healing is impaired in osteoporosis. Piper sarmentosum is a plant, which contains potent antioxidant, naringenin that may enhance fracture healing. The present histological study aimed to determine the effects of water extract of Piper sarmentosum on the late phase of fracture healing in estrogen-deficient rats.
METHODS: Twenty four female Sprague-Dawley rats (200-250 gm) were obtained. Six rats underwent sham operation and the rest were ovariectomized. Six weeks post-ovariectomy all the rats were fractured at the mid-diaphysis of the right femur and a K-wire was inserted for internal fixation. The sham group was given vehicle (normal saline) and the ovariectomized group was randomly subdivided into three groups: (i) ovariectomized-control group supplemented with vehicle; (ii) ovariectomized+estrogen replacement therapy group treated with estrogen (100 µg/kg/day) and (iii) ovariectomized+Piper sarmentosum group treated with Piper sarmentosum water extract (125 mg/kg). Following six weeks of treatment, the rats were sacrificed and the right femora were harvested for histological assessment of fracture callus.
RESULTS: The ovariectomized-control group showed a significant delay in fracture healing compared to the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups. The median callus score for the ovariectomized-Piper sarmentosum group was 4.50 (range, 4-5), which was significantly higher than the median callus score 3.50 (range, 3-4) for the ovariectomized-control group (P=0.019). However, there was no significant (P>0.05) difference in the callus score among the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups groups.
CONCLUSION: Treatment with water extract of Piper sarmentosum proved beneficial in the fracture healing in estrogen-deficient rats.
KEYWORDS: Antioxidant; callus; fracture healing; histology; osteoporosis; ovariectomy
Fulltext Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation

Ibrahim N', Khamis MF, Mod Yunoh MF, Abdullah S, Mohamed N, Shuid AN

PLoS One, 2014;9(12):e115595.
PMID: 25526611 DOI: 10.1371/journal.pone.0115595

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.
Fulltext Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency

Mohd Effendy N, Mohamed N, Muhammad N, Naina Mohamad I, Shuid AN

Evid Based Complement Alternat Med, 2012;2012:125761.
PMID: 22844328 DOI: 10.1155/2012/125761

Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.
Fulltext Nigella sativa: A Potential Antiosteoporotic Agent

Shuid AN, Mohamed N, Mohamed IN, Othman F, Suhaimi F, Mohd Ramli ES, et al.

Evid Based Complement Alternat Med, 2012;2012:696230.
PMID: 22973403 DOI: 10.1155/2012/696230

Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.

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