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Fulltext Supplementation of Stingless Bee Honey from Heterotrigona itama Improves Antiobesity Parameters in High-Fat Diet Induced Obese Rat Model

Mohd Rafie AZ, Syahir A, Wan Ahmad WAN, Mustafa MZ, Mariatulqabtiah AR

Evid Based Complement Alternat Med, 2018;2018:6371582.
PMID: 30643535 DOI: 10.1155/2018/6371582

Heterotrigona itama is a common stingless bee species found in Southeast Asia. Studies on the health benefits of its honey are limited in comparison with other stingless bee species. This study examines the antiobesity benefits found in stingless bee honey (SBH) from H. itama. The parameters used to measure the benefits were weight change, morphological structures, and biochemical characteristics. The research was conducted by using rats that were given a high-fat diet (HFD). In total 48 male Sprague Dawley (SD) rats were given a formulated HFD to increase the levels of obesity, the HFD was administered with a value of 0.68 g/cm2. The duration of the treatment was six weeks, and the results show that the induction obesity using the HFD was successful. Following this, the rats were then treated with SBH (at dosages of 1000 mg/kg, 750 mg/kg or 500 mg/kg), with orlistat or with a placebo. Compared with typical obesity treatment methods, the one that used the three dosages of SBH showed a higher reduction in body mass index (BMI), percentage of body weight gain, adiposity index, and relative organ weight (ROW). The levels of liver enzymes (ALT, AST, and ALP) were also significantly lower in SBH-treated groups. The levels of triglycerides and LDL-cholesterol were significantly lower, while the level of HDL-cholesterol was significantly higher in comparison with the control obese group. In terms of morphological structures, the number of adipocyte cells was reduced, and the hepatocytes found in the liver were less prone to rupturing when treated with SBH. In conclusion, the administration of SBH led to an improvement in indicators associated with obesity reduction. SBH also possesses a hepatoprotective potential which can reduce the health risks related to obesity.
Fulltext Combination of Epicatechin 3-Gallate from Euphorbia hirta and Cefepime Promotes Potential Synergistic Eradication Action against Resistant Clinical Isolate of Pseudomonas aeruginosa

Perumal S, Mahmud R, Mohamed N

Evid Based Complement Alternat Med, 2018;2018:5713703.
PMID: 30108657 DOI: 10.1155/2018/5713703

Pseudomonas aeruginosa is naturally resistant to many classes of antipseudomonal antibiotics due to the species ability to easily acquire resistance. Plant-based antibacterial agent in combination with the existing antibiotic proposes an alternative treatment regimen for the eradication of resistant bacterial infections. The antibacterial effects of the isolated epicatechin 3-gallate compound from Euphorbia hirta in combination with cefepime were investigated in vitro against resistant P. aeruginosa. The fractional inhibitory concentration index of the combination was determined using checkerboard broth microdilution method. Epicatechin 3-gallate combined with cefepime had produced synergistic effect against P. aeruginosa (with average FIC index of 0.24). The MIC of epicatechin 3-gallate was effectively reduced to MIC/4, MIC/8, MIC/16, and MIC/32 in the presence of cefepime. Time-kill study of epicatechin 3-gallate combined with cefepime exhibited remarkable bactericidal activity where the eradication of P. aeruginosa occurred within 4 h of treatment. Scanning electron micrographs revealed apparent cell membrane damage and leakage of cytoplasmic contents from P. aeruginosa cells which eventually led to the cell lysis after the combination treatment of epicatechin 3-gallate and cefepime. The potential of epicatechin 3-gallate to act synergistically with cefepime against clinically resistant P. aeruginosa strain possibly will maximize the successful outcomes when choosing empirical antibiotic treatment in hospitals or health care institutions.
Fulltext Medicinal Herbs and Their Active Compounds for Fatty Liver Diseases

Son CG, Wei Z, Raghavendran HB, Wang JH, Janda E

Evid Based Complement Alternat Med, 2017;2017:3612478.
PMID: 29362587 DOI: 10.1155/2017/3612478
Traditional Medicine for Wound Management

Suntar I, Sarker SD, Nahar L, Basar N

Evid Based Complement Alternat Med, 2017;2017:4214382.
PMID: 28798801 DOI: 10.1155/2017/4214382
Fulltext Role of Aromatherapy as a Natural Complementary and Alternative Therapy in Cardiovascular Disease: A Comprehensive Systematic Review

AlMohammed HI, A Alanazi N, Maghrabi EF, A Alotaibi M

Evid Based Complement Alternat Med, 2022;2022:4543078.
PMID: 35646155 DOI: 10.1155/2022/4543078

BACKGROUND: The purpose of this study was a comprehensive review of studies on the effect of aromatherapy with plant essential oils on the improvement of some conditions, for example, anxiety, stress, sleep quality, fatigue, and pain in people with cardiovascular disease.
MATERIALS AND METHODS: We carried out this systematic review based on the instructions of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Ethical agreement was not necessary as main data have not been collected. During March 2022, we searched the main English databases, for example, Google Scholar, Web of Sciences, EMBASE, EBSCO, ScienceDirect, Scopus, and PubMed/MEDLINE, with limitation to human clinical trials. For this study, no time limit was applied for the publication of articles.
RESULTS: Out of 1380 papers, 52 papers up to March 2022 were eligible for review in this systematic review. Based on the obtained results, the most widely used medicinal plants for aromatherapy in patients with cardiovascular diseases were Lavandula angustifolia (lavender, 55.7%), Rosa damascena (Damask rose, 11.5%), and Mentha piperita (peppermint, 5.8%), respectively. Most studies have been performed on the effect of aromatherapy on coronary angiography (21 papers, 40.4%), followed by artery bypass graft surgery (14 studies, 26.9%), and cardiac patients (5 studies, 9.6%). Most studies on the effect of aromatherapy in cardiovascular diseases were performed on anxiety (31 papers, 59.6%), sleep quality (8 studies, 15.4%), and hemodynamic parameters (6 studies, 11.5%), respectively.
CONCLUSION: This study systematically reviewed the effects of aromatherapy in patients with cardiovascular diseases. The review of studies showed that lavender, Damask rose, and peppermint are the most frequents plants used for aromatherapy, whereas they significantly improved some illnesses and conditions, especially anxiety and sleep quality. Therefore, it can be concluded that cardiologist can used aromatherapy as a natural complementary and alternative therapy particularly with lavender, Damask rose, and peppermint to improve quality of life and some conditions such as anxiety and sleep quality.
A Comprehensive Review with Future Prospects on the Medicinal Properties and Biological Activities of Curcuma caesia Roxb

Ibrahim NNA, Wan Mustapha WA, Sofian-Seng NS, Lim SJ, Mohd Razali NS, Teh AH, et al.

Evid Based Complement Alternat Med, 2023;2023:7006565.
PMID: 36704214 DOI: 10.1155/2023/7006565

Plants are the primary source of the food chain and are rich in nutrients and biochemical compounds that mainly give beneficial effects to humans as well as other living organisms. Curcuma caesia Roxb. is a family member of Zingiberaceae commonly known as black turmeric. The leaves and rhizomes of this plant are extensively used in Ayurvedic medicine and as traditional remedies for various ailments. The aromatic rhizomes and leaves are due to the presence of essential oils reported as camphor, ar-turmerone, (Z)-β-ocimene, ar-curcumene, 1,8-cineole, β-elemene, borneol, bornyl acetate, tropolone, ledol, β-elemenone, and α-bulnesene. Previous research studies have revealed most of the biological activities of C. caesia, such as antioxidant, antimicrobial, and anti-inflammatory properties, which are due to the presence of various bioactive components. The diverse chemical composition contained in this plant contributes to various biological activities, which may be beneficial for the health, food, and cosmetic industries. The purpose of this review was to summarise updated research on the in vitro and in vivo activities of C. caesia as well as the current clinical investigations. A compilation of the latest findings regarding the potential activities of C. caesia and mechanisms related to its health benefits is discussed and reviewed. This valuable information is the key that can be used for the development of drugs, functional food ingredients, and food products.
Fulltext Alpha-Mangostin Activates MOAP-1 Tumor Suppressor and Mitochondrial Signaling in MCF-7 Human Breast Cancer Cells

Simon SE, Lim HS, Jayakumar FA, Tan EW, Tan KO

Evid Based Complement Alternat Med, 2022;2022:7548191.
PMID: 35082905 DOI: 10.1155/2022/7548191

α-Mangostin, one of the major constituents of Garcinia mangostana, has been reported to possess several biological activities, including antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities associated with the inhibition of cell proliferation and activation of apoptosis. However, the cellular signaling pathway mediated by α-mangostin has not been firmly established. To investigate the cellular activities of α-mangostin, human cancer cells, MCF-7 and MCF-7-CR cells, were treated with α-mangostin to measure the cellular responses, including cytotoxicity, protein-protein interaction, and protein expression. Cancer cells stably expressed Myc-BCL-XL and HA-MOAP-1 were also included in the studies to delineate the cell signaling events mediated by α-mangostin. Our results showed that the apoptosis signaling mediated by α-mangostin involves the upregulation of endogenous MOAP-1, which interacts with α-mangostin activated BAX (act-BAX) while downregulating the expression of BCL-XL. Moreover, α-mangostin was found to induce BAX oligomerization, the release of mitochondrial cytochrome C, and activation of caspase in MCF-7 cells. In overexpression studies, MCF-7 cells and spheroids stably expressed HA-MOAP-1 and Myc-BCL-XL exhibited differential chemosensitivity toward α-mangostin in which the stable clones expressing HA-MOAP-1 and MYC-BCL-XL were chemosensitive and chemoresistant to the apoptosis signaling events mediated by α-mangostin, respectively, when compared to untreated cells. Together, the data suggest that the cytotoxicity of α-mangostin involves the activation of MOAP-1 tumor suppressor and its interaction with act-BAX, leading to mitochondria dysfunction and cell death.
Fulltext In Vitro Antiatherothrombotic Effects of Extracts from Berberis Vulgaris L., Teucrium Polium L., and Orthosiphon Stamineus Benth

Mohd Nor NH, Othman F, Mohd Tohit ER, Md Noor S, Razali R, Ahmad Hassali H, et al.

Evid Based Complement Alternat Med, 2019;2019:3245836.
PMID: 31001352 DOI: 10.1155/2019/3245836

Coronary artery disease is the leading cause of mortality and morbidity worldwide. The pathogenesis is mainly due to atherosclerosis, plaque rupture, and platelet thrombus formation. The main risk factors for coronary artery disease include obesity, hypercholesterolemia, smoking, diabetes, and high blood pressure. As a part of disease management, treatment options using anticoagulant and antiplatelet drugs can be applied with addition to lipid-lowering medication. However, medicinal plants comprising antiatherothrombotic effects can be used as options to combat the disease rather than drug therapies with lesser adverse effects. Therefore, the haematological effect of Berberis vulgaris L., Teucrium polium L., and Orthosiphon stamineus Benth extracts was studied using in vitro model to prevent and to treat coronary atherothrombotic disease. The aqueous, methanol, and polysaccharide extracts of B. vulgaris, T. polium, and O. stamineus, respectively, were studied for their anticoagulant and antiplatelet effect on human whole blood. Extracts were subjected to the prothrombin time (PT) and activated partial thromboplastin time (APTT) test for anticoagulant activity. The antiplatelet activity was investigated using an electrical impedance method. B. vulgaris aqueous extract (BVAE), B. vulgaris polysaccharide extract (BVPE), T. polium aqueous extract (TPAE), and T. polium polysaccharide extract (TPPE) significantly prolonged the coagulation time in a concentration-dependent manner (p<0.05). The administration of BVAE demonstrated the most effective antiplatelet activity against platelet aggregation caused by arachidonic acid (AA) and collagen. These antiplatelet activities may correspond to the presence of higher total phenolic compound, which thus inhibit the platelet aggregation activity. In conclusion, these findings provide strong evidence on the antiatherothrombotic effect of BVAE and TPAE.
Fulltext Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

Alexander HR, Syed Alwi SS, Yazan LS, Zakarial Ansar FH, Ong YS

Evid Based Complement Alternat Med, 2019;2019:9725738.
PMID: 31915456 DOI: 10.1155/2019/9725738

Wound healing is a regulated biological event that involves several processes including infiltrating leukocyte subtypes and resident cells. Impaired wound healing is one of the major problems in diabetic patients due to the abnormal physiological changes of tissues and cells in major processes. Thymoquinone, a bioactive compound found in Nigella sativa has been demonstrated to possess antidiabetic, anti-inflammatory, and antioxidant effects. Today, the rapidly progressing nanotechnology sets a new alternative carrier to enhance and favour the speed of healing process. In order to overcome its low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aimed to determine the effect of TQ-NLC and TQ on cell proliferation and migration, mode of cell death, and the antioxidant levels in normal and diabetic cell models, 3T3 and 3T3-L1. Cytotoxicity of TQ-NLC and TQ was determined by MTT assay. The IC10 values obtained for 3T3-L1 treated with TQ-NLC and TQ for 24 hours were 4.7 ± 3.3 and 5.3 ± 0.6 μM, respectively. As for 3T3, the IC10 values obtained for TQ-NLC and TQ at 24 hours were 4.3 ± 0.17 and 3.9 ± 2.05 μM, respectively. TQ-NLC was observed to increase the number of 3T3 and 3T3-L1 healthy cells (87-95%) and gradually decrease early apoptotic cells in time- and dose-dependant manner compared with TQ. In the proliferation and migration assay, 3T3-L1 treated with TQ-NLC showed higher proliferation and migration rate (p < 0.05) compared with TQ. TQ-NLC also acted as an antioxidant by reducing the ROS levels in both cells after injury at concentration as low as 3 μM. Thus, this study demonstrated that TQ-NLC has better proliferation and migration as well as antioxidant effect compared with TQ especially on 3T3-L1 which confirms its ability as a good antidiabetic and antioxidant agent.
Fulltext Detarium microcarpum, Guiera senegalensis, and Cassia siamea Induce Apoptosis and Cell Cycle Arrest and Inhibit Metastasis on MCF7 Breast Cancer Cells

Adebayo IA, Gagman HA, Balogun WG, Adam MAA, Abas R, Hakeem KR, et al.

Evid Based Complement Alternat Med, 2019;2019:6104574.
PMID: 31239861 DOI: 10.1155/2019/6104574

Despite the availability of anticancer drugs, breast cancer remains the most death-causing tumor-related disease in women. Hence, there is a need for discovery and development of efficient alternative drugs, and sources such as plants need to be explored. In this study, antioxidant capacities and inhibitory effects against MCF7 cells of the extracts of stem bark of three Nigerian medicinal plants (Detarium microcarpum, Guiera senegalensis, and Cassia siamea) were investigated. The D. microcarpum extracts had the highest antioxidant and antiproliferative effects, followed by that of G. senegalensis, and the C. siamea extracts had minimal effects. The IC50 values of the methanol and aqueous extracts from the three plants that inhibited the proliferation of MCF7 cells ranged from 78-> 500 μg/ml. Moreover, all the plant extracts but the aqueous extract of Cassia siamea exhibited antimetastatic action and induced apoptosis and cell cycle arrest in MCF7 cells. Liquid chromatography/time-of-flight/mass spectrometry profiling revealed that the five potent extracts contain many phenols and omega-6 fatty acids, and some of the identified compounds (isorhamnetin, eupatorin, alpinumisoflavone, procyanidin B3, syringin, and gallic acid) have been reported to have antiproliferative effects on cancer cells. Hence, the stem bark of these plants could be potential sources of antibreast cancer agents.
Fulltext Exploring the Potential Use of Hylocereus polyrhizus Peels as a Source of Cosmeceutical Sunscreen Agent for Its Antioxidant and Photoprotective Properties

Vijayakumar R, Abd Gani SS, Zaidan UH, Halmi MIE, Karunakaran T, Hamdan MR

Evid Based Complement Alternat Med, 2020;2020:7520736.
PMID: 32454871 DOI: 10.1155/2020/7520736

Currently, consumers' demand for sunscreens derived from natural sources that provide photoprotection from ultraviolet (UV) radiation is pushing the cosmetic industry to develop breakthrough formulations of sun protection products by incorporating plant antioxidants as their active ingredients. In this context, the present study was initiated to evaluate the antioxidant and photoprotective properties of the underutilized Hylocereus polyrhizus peel extract (HPPE) using in vitro spectrophotometric techniques. The phytochemical screenings of HPPE conducted via high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) revealed the presence of phenolic acids and flavonoids as the major secondary metabolites in HPPE. The antioxidant potentials evaluated based on 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and total antioxidant capacity assays were in the range of 22.16 ± 0.24%-84.67 ± 0.03% with 50% inhibitory concentration (IC50) of 36.39 ± 0.04 μg/mL and 23.76 ± 0.14%-31.87 ± 0.26% (IC50 = 21.93 ± 0.07 μg/mL), respectively. For the photoprotective evaluation, the results showed that HPPE had significantly high absorbance values (3.1-3.6) at 290-320 nm with an exceptional sun protection factor (SPF) value of 35.02 ± 0.39 at 1.00 mg/mL. HPPE also possessed a broad-spectrum shielding power against both UVA and UVB radiations. Hence, in terms of practical implications, our findings would offer an exciting avenue to develop a photoprotective formulation incorporating the ethanolic extract of Hylocereus polyrhizus peels as a synergistic active ingredient for its excellent UV absorption properties and the strong antioxidant activities.
Fulltext Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil

Ahmad Nazri KA, Fauzi NM, Buang F, Mohd Saad QH, Husain K, Jantan I, et al.

Evid Based Complement Alternat Med, 2019;2019:7246756.
PMID: 31662779 DOI: 10.1155/2019/7246756

Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p < 0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p < 0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.
Fulltext Potency of Selected Berries, Grapes, and Citrus Fruit as Neuroprotective Agents

Tan SJ, Ismail IS

Evid Based Complement Alternat Med, 2020;2020:3582947.
PMID: 32565853 DOI: 10.1155/2020/3582947

A healthy diet should nourish the brain with essential nutrients, including bioactive compounds, for normal brain functioning and to protect it from the negative effects of inflammation and oxidative stress. In this review, a concise summation of the protective effects of selected fruits, namely, berries, grapes, and citrus fruits, against neurological disorder is presented. The focus is on the neuroprotective potential of these fruits against neurodegenerative and mental disorders. The fruits selection was based on the vast reported pharmacological studies on their neuroprotection efficacies. Hence, the respective knowledge and limitations are discussed based on the biological and pharmacological evidence compiled from the previously reported laboratory, epidemiology, and intervention trials.
Fulltext Evaluation of Antioxidant and Wound Healing Effects of Alcoholic and Aqueous Extract of Ocimum sanctum Linn in Rats

Shetty S, Udupa S, Udupa L

Evid Based Complement Alternat Med, 2008 Mar;5(1):95-101.
PMID: 18317555 DOI: 10.1093/ecam/nem004

In recent years, oxidative stress and free radicals have been implicated in impaired wound healing. Ocimum sanctum (O. sanctum), a plant widely used in Ayurveda, possesses anti-inflammatory and antioxidant properties. The present study was undertaken to assess the potential of alcoholic and aqueous extracts in wound healing in Wistar albino rats. The rats were divided into five groups of six animals each. Group 1 is normal wounded control and the other four groups were treated with two different doses each of alcoholic and aqueous extract of O. sanctum. The wound healing parameters were evaluated by using incision, excision and dead space wounds in extract-treated rats and controls. Both the doses of alcoholic and aqueous extract significantly increased wound breaking strength, hydroxyproline, hexuronic acid, hexosamines, superoxide dismutase, catalase, reduced glutathione and significantly decreased percentage of wound contraction and lipid peroxidation when compared with the control group. The results suggest that O. sanctum has antioxidant properties, which may be responsible and favorable for faster wound healing and this plant extract may be useful in the management of abnormal healing and hypertropic scars.
Fulltext Hypoglycemic Effects of Plant Flavonoids: A Review

Sok Yen F, Shu Qin C, Tan Shi Xuan S, Jia Ying P, Yi Le H, Darmarajan T, et al.

Evid Based Complement Alternat Med, 2021;2021:2057333.
PMID: 34925525 DOI: 10.1155/2021/2057333

Diabetes mellitus is a metabolic disorder with chronic high blood glucose levels, and it is associated with defects in insulin secretion, insulin resistance, or both. It is also a major public issue, affecting the world's population. This disease contributes to long-term health complications such as dysfunction and failure of multiple organs, including nerves, heart, blood vessels, kidneys, and eyes. Flavonoids are phenolic compounds found in nature and usually present as secondary metabolites in plants, vegetables, and fungi. Flavonoids possess many health benefits such as anti-inflammatory and antioxidant activities, and naturally occurring flavonoids contribute to antidiabetic effects.Many studies conducted in vivo and in vitro have proven the hypoglycemic effect of plant flavonoids. A large number of studies showed that flavonoids hold positive results in controlling the blood glucose level in streptozotocin (STZ)-induced diabetic rats and further prevent the complications of diabetes. The future development of flavonoid-based drugs is believed to provide significant effects on diabetes mellitus and diabetes complication diseases. This review aims at summarizing the various types of flavonoids that function as hyperglycemia regulators such as inhibitors of α-glucosidase and glucose cotransporters in the body. This review article discusses the hypoglycemic effects of selected plant flavonoids namely quercetin, kaempferol, rutin, naringenin, fisetin, and morin. Four search engines, PubMed, Google Scholar, Scopus, and SciFinder, are used to collect the data.
Fulltext Effective Antiplasmodial and Cytotoxic Activities of Synthesized Zinc Oxide Nanoparticles Using Rhazya stricta Leaf Extract

Najoom S, Fozia F, Ahmad I, Wahab A, Ahmad N, Ullah R, et al.

Evid Based Complement Alternat Med, 2021;2021:5586740.
PMID: 34484393 DOI: 10.1155/2021/5586740

In the present study, zinc oxide (ZnO) nanoparticles were prepared using ZnCl2.2H2O as a precursor, via green route using leaf extract of Rhazya stricta as capping and reducing agent. The prepared ZnO nanoparticles were examined using UV-visible spectrophotometer (UV-Vis), Fourier transform infrared spectrometer (FT-IR), X-ray diffraction spectrometer (XRD), and scanning electron microscope (SEM). The UV-Vis absorption spectrum at 355 nm showed an absorption peak, which indicates the formation of ZnO NPs. The FT-IR spectra analysis was performed to identify the potential biomolecule of the as-prepared ZnO NPs. The FT-IR spectra showed peaks at 3455, 1438, 883, and 671 cm-1 in the region of 4000-500 cm-1, which indicates -OH, NH, C-H, and M-O groups, respectively. The SEM images showed aggregation of ZnO nanoparticles with an average size of 70-90 nm. The XRD study indicated that the ZnO NPs were crystalline in nature with hexagonal wurtzite structure and broad peaks were observed at 2 theta positions 31.8°, 34.44°, 36.29°, 47.57°, 56.61°, 67.96°, and 69.07°. The synthesized ZnO NPs were found to be good antiplasmodial with a 50% inhibitory concentration (IC50) value of 3.41 μg/mL. It is concluded from the current study that the ZnO NPs exhibited noble antiplasmodial activity, and for the improvement of antiplasmodial medications, it might be used after further in vivo studies.
Systematic Review of Medicinal Plants Used for Treatment of Diabetes in Human Clinical Trials: An ASEAN Perspective

Salleh NH, Zulkipli IN, Mohd Yasin H, Ja'afar F, Ahmad N, Wan Ahmad WAN, et al.

Evid Based Complement Alternat Med, 2021;2021:5570939.
PMID: 34691218 DOI: 10.1155/2021/5570939

Traditionally, there are some medicinal plants believed to treat diabetes, as they have been proven in research studies to possess antidiabetic properties, such as improved insulin sensitivity and hypoglycemic activities, due to their high level of phenolic compounds, flavonoids, terpenoids, alkaloids, and glycosides. We conducted a systematic review to identify potential medicinal plants used during human clinical trials in the Association of Southeast Asian Nation (ASEAN) countries on prediabetic or type 2 diabetic individuals and to potentially identify any bioactive compounds involved in effectively treating symptoms of diabetes such as lowering of blood glucose. A total of 1209 reference titles were retrieved from four selected databases (Science Direct, Scopus, Springer Link, and PubMed) and only three met the inclusion criteria. Upon evaluation of the selected articles, four medicinal plants were identified: turmeric (Curcuma longa), garlic (Allium sativum L.), bitter melon (Momordica charantia), and Rosella flower (Hibiscus sabdariffa L.). Of these, only the bitter melon study did not show any significant change in the blood glucose of participants after intervention. This review demonstrates the limitations in published articles of human clinical trials for medicinal plants' intervention for diabetes. Upon further investigations on the four identified medicinal plants included in the animal studies, the findings showed positive effects in the management of diabetes, such as hyperglycemia. Hence, further testing and standardization of the methods in the studies can be suggested for human clinical trials for reliable data collections such as methods of extract preparation, duration of intervention, and conditions set for the study design.
Fulltext Chemical Composition, Pharmacological, and Toxicological Effects of Betel Nut

Chen X, He Y, Deng Y

Evid Based Complement Alternat Med, 2021;2021:1808081.
PMID: 34457017 DOI: 10.1155/2021/1808081

Betel nut, the fruit of Areca catechu L, has a long medical history in Southeast Asia. It is native to Malaysia and is cultivated and processed extensively in subtropical regions, such as South China and India. Betel nut almost appears as a "snack" in various occasions in most parts of China. Clinically, betel nut can play a certain pharmacology role and was used in malaria, ascariasis, arthritis, enterozoic abdominalgia, stagnation of food, diarrhea, edema, and beriberi. The nervous excitement of betel nut chewing has made it gradually become popular. However, chewing betel nut can induce oral submucosal fibrosis (OSF) and oral cancer (OC). At the same time, long-term chewing of betel nut also causes inhaled asthma, sperm reducing, betel quid dependence (BQD), and uterine and esophageal cancers. The main components of processed betel nut are the goal of this review. This study will mainly start from the pharmacological activity and toxicology study of betel nut in recent years, aiming to seek its advantages and disadvantages. In the meantime, this study will analyze and emphasize that betel nut and arecoline are the high-risk factors for oral cancer, which should arouse attention and vigilance of the public.
Synergistic Cytotoxicity between Elephantopus scaber and Tamoxifen on MCF-7-Derived Multicellular Tumor Spheroid

Ho WY, Liew SS, Yeap SK, Alitheen NB

Evid Based Complement Alternat Med, 2021;2021:6355236.
PMID: 34712346 DOI: 10.1155/2021/6355236

Elephantopus scaber Linn, a traditional herb, exhibited anticancer properties, and it was cytotoxic against the monolayer estrogen receptor-positive breast cancer cell line, MCF-7, in the previous study. In order to determine the potential of E. scaber as a complementary medicine for breast cancer, this study aimed to evaluate the synergism between E. scaber and tamoxifen in cytotoxicity using MCF-7 in the form of 3-dimensional multicellular tumor spheroid (MCTS) cultures. MCTS represents a more reliable model for studying drug penetration as compared to monolayer cells due to its greater resemblance to solid tumor. Combination of E. scaber ethanol extract and tamoxifen, which were used in concentrations lower than their respective IC50 values, had successfully induced apoptosis on MCTS in this study. The combinatorial treatment showed >58% increase of lactate dehydrogenase release in cell media, cell cycle arrest at the S phase, and 1.3 fold increase in depolarization of mitochondrial membrane potential. The treated MCTS also experienced DNA fragmentation; this had been quantified by TUNEL-positive assay, which showed >64% increase in DNA damaged cells. Higher externalization of phospatidylserine and distorted and disintegrated spheroids stained by acridine orange/propidium iodide showed that the cell death was mainly due to apoptosis. Further exploration showed that the combinatorial treatment elevated caspases-8 and 9 activities involving both extrinsic and intrinsic pathways of apoptosis. The treatment also upregulated the expression of proapoptotic gene HSP 105 and downregulated the expression of prosurvival genes such as c-Jun, ICAM1, and VEGF. In conclusion, these results suggested that the coupling of E. scaber to low concentration of tamoxifen showed synergism in cytotoxicity and reducing drug resistance in estrogen receptor-positive breast cancer.
Fulltext Effect of Huanglian Decoction on the Intestinal Microbiome in Stress Ulcer (SU) Mice

Zhang Q, Guo JJ, Yau YM, Wang YJ, Cheng YB, Tuo X, et al.

Evid Based Complement Alternat Med, 2021;2021:3087270.
PMID: 34603467 DOI: 10.1155/2021/3087270

Background: Stress ulcer (SU) is a serious gastrointestinal mucosal lesion under acute stress. Huanglian decoction is a famous traditional Chinese medicine prescription, which has been used to treat digestive system diseases for thousands of years. Many clinical cases have proved that Huanglian decoction has a good effect on SU. Some studies have shown that the intestinal bacteria will be changed accordingly when the gastrointestinal mucosa is damaged. However, there are few published reports on the effect of the intestinal microbiome with SU mice that were treated by Huanglian decoction. In this study, we investigated the effect of the fecal microbiome in mice with SU by the 16S rDNA sequencing technology.
Methods: Male KM mice were induced by cold-restraint stress except for the normal control group and then treated by Huanglian decoction (Group HD) and Esomeprazole magnesium solution (Group ES) separately for 7 days. 16S rDNA sequencing technology analysis was applied to evaluate the changes of bacterial flora in mice feces. And, histopathological methods and molecular biological detection methods were also performed.
Results: Huanglian decoction could help to repair the gastric mucosal injury and regulate the relative content of TNF-α and IL-1β. Moreover, Huanglian decoction could increase the relative abundance of intestinal probiotics in the intestine of mice with SU, especially in Verrucomicrobiae and Akkermansia.
Conclusions: Huanglian decoction might effectively promote the repair of gastrointestinal mucosal injury and regulate the number and species of intestinal bacteria to maintain the stability of gastrointestinal microecology.

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