Loh Yean Chun
@usm.my
School of Chemical Sciences
Universiti Sains Malaysia
RESEARCH INTERESTS
Research mainly focus on 1. Antihypertensive agents (TCMH/pure compounds) 2. Pain research (analgesic meter for pain model research) 3. Local herbs Pharmacopoeia 4. Vascular tone research (vasorelaxant/vasoconstrictor) 5. Anti-radiation research
Scopus Publications
Scopus Publications
Tiejun Zhang, Huarong Liu, Yi Lu, Qinglei Wang, Yean Chun Loh, and Zeyun Li
Elsevier BV
Yean Chun Loh, Chuan Wei Oo, Wan Yin Tew, Xu Wen, Xu Wei, and Mun Fei Yam
Elsevier BV
Yean Chun Loh, Chuan Wei Oo, Wan Yin Tew, and Mun Fei Yam
Korean Pharmacopuncture Institute
Healthcare has always been a crucial component of a highquality lifestyle for humanity. It has recently become a significant concern due to the growing number of infectious diseases, including the recent outbreak of Coronavirus disease 2019 (COVID-19) and the rapidly increasing rates of chronic illnesses in youngsters [1]. This has ignited global concerns about the need to continue looking for effective and alternative treatments, leading to the appearance of a global rallying team that is evaluating the pharmacological effects of wellor partially known active compounds using the conventional mechanismcentred research paradigm, which involves in vitro and in vivo research models and mechanism of action studies. However, the difficulty of translating this research into clinical and practice has gradually become apparent in modern-drug research. Therefore, we, as scientists, should aim to determine an effective way to increase translation efficacy from research into practice. For instance, over two hundred studies were conducted using in vitro approaches to evaluate the vasorelaxation effects of various phytochemicals and their mechanistic actions to discover a new antihypertensive drug [2]. Although all of these studies claimed their compounds exhibited a relatively strong vasorelaxant effect in vitro, most of them were stopped at the same phase and were not further implemented in real-life medical practice. We, of course, understand that the key advantage of in vitro research is that it is free of the drawbacks of animal testing and uses a relatively low-cost model. Nevertheless, when compounds are administered into the human body, which has multiple pathways and constant communication among cells, various unknown reactions will occur, greatly affecting the therapeutic effects in comparison with those claimed in vitro [3]. Moreover, the chemical characteristics of compounds, such as poor chemical stability and low bioavailability, can be another limiting factor in proceeding with their use in real-life medical practice [4]. These factors drastically reduced the potential of these tested compounds to be successfully translated into current medical practice. In our view, an evidence-based research approach can be seen as a potential trend in pharmacological research to improve the effectiveness of research translation into practice. The evidence here refers to the knowledge of safety and efficacy that has been clinically demonstrated in humans. Scientists often emphasise the importance of phytochemicals in drug discovery research since herbs are the most natural repository of supple-
W.H. Liu, Z-Y Li and Y. C. Loh
OBJECTIVE
The aim of the study was to evaluate the effect of a hot environment on several physiological variables of soccer players and suggest feasible solutions to it.
SUBJECTS AND METHODS
The study is of prospective design, considering 66 participants comprising professional soccer players. All the participants completed the Physical Activity Readiness Questionnaire (PARQ). The participants were assigned to 3 different groups. Each group was assigned 22 participants. They were made to play in three different chambers, maintained at cool, moderate and hot temperatures. Players were made to play and various variables were determined to assess the effect of hot temperature on them.
RESULTS
Several variables were determined including absolute and relative oxygen uptake, heart rate, minute ventilation, the blood concentration of lactate and time to get exhausted. All the variables of players who played in hot temperatures have revealed higher heart rate, ventilation and increased lactate concentration. Players in a hot environment ran out faster.
CONCLUSIONS
The study was concluded due to the players' dehydration and physiological deteriorated factors in a hot environment, leading to poor performances and also affecting the players' health in the long run. Further, the study suggested improving the environment around the game venues.
Y. Fan, Z-Y Li and Y. C. Loh
OBJECTIVE
The aim of the study was to find the significance of several factors with parameters of urine tests and blood tests. Finally, we aimed at evaluating the percentage of athletes from the study sample regarding their hydration level.
SUBJECTS AND METHODS
The current study is the prospective type and was conducted on Chinese athletes between June 2021 to April 2022. The study was done in 2 parts for obtaining measurements in the summer season and the winter season and then they were correlated between them. Urine and blood samples were evaluated for determining the required parameters. The parameters of the physical environment like temperature, relative humidity, precipitation, etc. were obtained from the concerned weather station for each day.
RESULTS
It was observed that 14.5%, 59% and 26.5% of the female participants were found to have hyper-hydrated, euhydrated and dehydrated, respectively. While 17.57%, 69.69% and 12.74% of the males were classified as hyper-hydrated, euhydrated and dehydrated, respectively. The participants with hyper-hydrated were found to have increased urine volume (p<0.001), reduced specific gravity (p<0.001) and reduced-sodium level (p<0.001).
CONCLUSIONS
The study found that there is a significant difference in sodium levels between gender and seasons. The level of serum osmolality is also significantly different between the whole study populations concerning combined seasons. In this way, many other parameters are evaluated by correlation with seasons and gender. Hence, this study has brought forward various important findings and gives an overall evaluation of hydration status.
Yean Chun Loh, Sock Ying Chan, C. Oo and M. Yam
AIMS
The structure-vasorelaxant activity relationships (SARs) assessment in previous study has found that trans-3,4,4'-trihydroxystilbene (344OH) could potentially act as a vasorelaxing agent with demonstration of over 2-fold maximal relaxation (Rmax) compared to its analogue, resveratrol. The present study focuses on the mechanism of actions and pathways employed by 344OH and compared to its analogue to further speculate the SAR of stilbenoids towards vasorelaxation.
MATERIALS AND METHODS
The 344OH employed in present study was synthesized based on the protocol in previous study. The vascular responses towards the cumulative addition of 344OH were evaluated using in vitro rat aortic rings assays.
KEY FINDINGS
The pEC50 and Rmax values were found to be 4.33 ± 0.05 and 106 ± 3.99%, respectively. Results showed that the vasorelaxation of 344OH were predominated by G-protein-coupled muscarinic- (M3) and β2-adrenergic receptors, followed by PGI2/AC/cAMP- and NO/sGC/cGMP-dependent pathways. It was also identified that 344OH employed voltage-activated- (Kv), calcium-activated- (Kca) and inwardly-rectifying (Kir) potassium channels and act as an antagonist for both VOCC and IP3R while regulating the action potential in the vasculature.
SIGNIFICANCE
The different position of hydroxyl substituent located in A-ring of the stilbenoid backbone in 344OH compared to resveratrol resulted in a significant difference in mechanistic actions that lead to 344OH's fast-acting and less time-dependent vasorelaxation behaviour. This has substantially increased the potential of 344OH to be developed as an effective antihypertensive drug in future. Present findings further strengthen our inferences where the SARs study approach should be carried out as the mainstream methodology in future drug development research.
Yeong Hui Lim, Chuan Wei Oo, Rhun Yian Koh, Gah Leong Voon, Mei Yeng Yew, Mun Fei Yam, and Yean Chun Loh
Wiley
In recent years, chalcones and their derivatives have become the focus of global scientists due to increasing evidence reported towards their potency in antitumor and anti‐cancer. Here, the chalcones designed and synthesized in our present study were derived from the derivatives of naphthaldehyde and acetophenone. Both these precursors have been reported in demonstrating a certain degree of anticancer property. Also, the substituents on these precursors such as hydroxyl, methoxy, prenyl, and chloro were shown able to enhance the anticancer efficiency. Hence, it is the interest of the current study to investigate the anticancer potential of the hybrid molecules (chalcones) consisting of these precursors with different alkoxy substituents and with or without the fluorine moiety. Two series of chalcone derivatives were designed, synthesized, and characterized using the elemental analysis, IR, 1H and 13C NMR spectroscopy, subsequently evaluated for their anti‐cancer activity. Interestingly, the results showed that the fluorinated chalcones 11–15 exhibited stronger cytotoxic activity towards the breast cancer cell lines (4T1) compared to non‐fluorinated chalcone derivatives. Remarkably, the selectivity index obtained for these fluorinated chalcones derivatives against the breast cancer 4T1 cell line was higher than those exhibited by cisplatin, which is one of the most frequently deployed chemotherapy agents in current medical practice. These findings could provide an insight towards the potential of fluorinated chalcones being developed as an anti‐cancer agent with moderate activity towards breast cancer cell and low inhibition of fibroblast cell at a concentration of 100 μM.
Sock Ying Chan, Yean Chun Loh, Chuan Wei Oo, and Mun Fei Yam
Elsevier BV
The development of vasorelaxant as the antihypertensive drug is important as it produces a rapid and direct relaxation effect on the blood vessel muscles. Resveratrol (RV), as the most widely studied stilbenoid and the lead compound, inducing the excellent vasorelaxation effect through the multiple signalling pathways. In this study, the in vitro vascular response of the synthesized trans-stilbenoid derivatives, SB 1-8e were primarily evaluated by employing the phenylephrine (PE)-precontracted endothelium-intact isolated aortic rings. Herein we report trans-3,4,4'-trihydroxystilbene (SB 8b) exhibited surprisingly more than 2-fold improvement to the maximal relaxation (Rmax) of RV. This article also highlights the characterization of the aromatic protons in terms of their unique splitting patterns in 1H NMR.
Chu Shan Tan, Yeah Chun Loh, Wan Yin Tew, and Mun Fei Yam
Springer Science and Business Media LLC
Resveratrol is found in numerous plant-based foods and beverages and is known to have an impact on the cardiovascular system. The aim of this study was to investigate the vasorelaxant effect of resveratrol and its underlying mechanisms by employing an aortic ring assay model. Resveratrol caused relaxation of aortic rings that had been precontracted with phenylephrine in the presence of endothelium or with potassium chloride in endothelium-intact aortic rings. The vasorelaxant effect was decreased in the absence of an endothelium. The mechanisms underlying the vasorelaxant effect of resveratrol were determined through the addition of antagonists. In the presence of the endothelium, indomethacin (a nonselective cyclooxygenase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor), Nω-nitro-l-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), tetraethylammonium (TEA, nonselective calcium activator potassium channel blocker), 4-aminopyridine (4-AP, voltage-dependent K+ channel blocker), barium chloride (BaCl2, inwardly rectifying K+ channel blocker), glibenclamide (non-specific ATP-sensitive K+ channel blocker) and propranolol (β-adrenergic receptor blocker) led to a significant reduction in the vasorelaxation effect induced by resveratrol. Resveratrol was also found to reduce Ca2+ release from the sarcoplasmic reticulum and block calcium channels. In conclusion, resveratrol targets multiple signalling pathways for exerting its vasorelaxant effects in the rat aortic ring model in both the presence and absence of endothelium.
Mun Fei Yam, Yean Chun Loh, Chuan Wei Oo, and Rusliza Basir
MDPI AG
Pain is the most common sensation installed in us naturally which plays a vital role in defending us against severe harm. This neurological mechanism pathway has been one of the most complex and comprehensive topics but there has never been an elaborate justification of the types of analgesics that used to reduce the pain sensation through which specific pathways. Of course, there have been some answers to curbing of pain which is a lifesaver in numerous situations—chronic and acute pain conditions alike. This has been explored by scientists using pain-like behavioral study methodologies in non-anesthetized animals since decades ago to characterize the analgesic profile such as centrally or peripherally acting drugs and allowing for the development of analgesics. However, widely the methodology is being practiced such as the tail flick/Hargreaves test and Von Frey/Randall–Selitto tests which are stimulus-evoked nociception studies, and there has rarely been a complete review of all these methodologies, their benefits and its downside coupled with the mechanism of the action that is involved. Thus, this review solely focused on the complete protocol that is being adapted in each behavioral study methods induced by different phlogogenic agents, the different assessment methods used for phasic, tonic and inflammatory pain studies and the proposed mechanism of action underlying each behavioral study methodology for analgesic drug profiling. It is our belief that this review could significantly provide a concise idea and improve our scientists’ understanding towards pain management in future research.
Yean Chun Loh, Sock Ying Chan, Chuan Wei Oo and M. Yam
This paper meets the requirements of KS X ISO 9706, ISO 9706-1994 and ANSI/NISO Z39.48-1992 (Permanence of Paper). *Corresponding Author Chuan Wei Oo. School of Chemical Sciences, Universiti Sains Malaysia, Malaysia. Tel.: +60-4653-3680 E-mail: oocw@usm.my Mun Fei Yam, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Malaysia. Tel: +60-4653-4586 E-mail: yammunfei@yahoo.com c 2020 Korean Pharmacopuncture Institute http://www.journal-pharm.com Creation of Novel Antihypertensive Agent via Structure-Activity Relationship Study on Phytochemicals towards Vasorelaxant Activity
Yean Chun Loh, Sock Ying Chan, Wan Yin Tew, Chuan Wei Oo, and Mun Fei Yam
Elsevier BV
Hypertension is one of the leading causes of mortality in relation to the cardiovascular conditions and easily the most overlooked and poorly managed disease in mankind. With well over 200 drugs available in the market globally, there is still an urgency to search for antihypertensive alternatives due to the subpar efficacy and unwarranted side effects of the current choices. Present studies reported over 250 types of plant-derived compounds were being investigated for potential pharmacological effects on the vasculature in the last 3 decades. There were numerous literatures that claimed various compounds exhibiting vasorelaxant properties to a certain extent with low numbers of these compounds being successfully adapted into the current medicinal practice for treatment of hypertension. The issue is the scarcity of reviews that summarizes the discovery of this field and the lack of thorough comparison of these compounds to identify which of these vasodilators should be the next face of hypertension management. Thus, this review is aiming towards identifying the relationship between a major class of plant-derived compounds, flavonoid's activity as a vasodilator with their signalling pathways and their structural characteristics according to their vasorelaxant properties. Interestingly, we found that both nitric oxide and voltage-operated calcium channels pathways, and two of the flavonoid's structural characteristics play crucial roles in eliciting strong vasorelaxant effects. We have faith that the insights of this review will serve as a reference for those researching similar topics in the future and potentially lead to the development of more promising antihypertensive alternative.
Chu Shan Tan, Chiew Hoong Ng, Yean Chun Loh, and Mun Fei Yam
Springer Science and Business Media LLC
One of the traditional folk medicine in the Malaysia is using porcupine bezoar. It was reported as universal medicine in ancient time. This bezoar has been a myth to the locals. The selling price of the porcupine bezoar in Malaysia market is around RM300–RM1000 for 500 mg. The widespread use of the bezoar as an alternative medicine for treatment of deadly illnesses in Malaysia was passed down from generations of the multi-diverse ethnicity environment that existed here. Additionally, porcupine bezoar was also known as lifesaver and used by patients with terminal illness. Porcupine bezoar was found in the gastrointestinal tract of porcupine and made up of indigestible plant matters. Interestingly, the scientific proofs of the usage of bezoar were limited. The chemical profile and the medicinal properties of the bezoar is still unknown. The main focus of this review paper is on the porcupine bezoar which can be found in Malaysia.
Chu Shan Tan, Yean Chun Loh, Yung Sing Ch’ng, Chiew Hoong Ng, Zhao Qin Yeap, Mariam Ahmad, Mohd Zaini Asmawi, and Mun Fei Yam
Elsevier BV
ETHNOPHARMACOLOGICAL RELEVANCE
Citrus reticulatae Pericarpium (Chen pi) was widely used as an important ingredient in the prescription of TCM to treat phlegm fluid retention type hypertension. Since Chen pi is involved in treatment as antihypertensive TCM formula, we have reasonable expectation in believing that it might possess vasorelaxant activity.
AIM OF THE STUDY
This study is designed to investigate the vasorelaxant effect of Chen pi and to study its pharmacology effects.
MATERIALS AND METHODS
The vasorelaxant effect of water extract of Chen pi (CRW) were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. The fingerprint of Chen pi and the extracts were developed with quantification of hesperidin content by HPTLC.
RESULTS
CRW exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro-L-arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV blocker), barium chloride (Kir blocker), and glibenclamide (KATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing Ca2+ releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels.
CONCLUSION
The vasorelaxant effect of CRW on rat aorta involves NO/sGC, calcium and potassium channels, muscarinic and β-adrenergic receptors.
Yean Chun Loh, Chu Shan Tan, Yung Sing Ch’ng, Chiew Hoong Ng, Zhao Qin Yeap, and Mun Fei Yam
Springer Science and Business Media LLC
Panax notoginseng is the most valuable medicinal plant and has been used clinically for more than two thousand years to treat various diseases, including hypertension. Previous studies claimed that different isolated compounds from P. notoginseng are involved in different pathways for vasodilation. It is strongly believed that these vasodilating compounds might act synergistically in contributing vasodilatory effects via holistic signaling pathways. The present study aims to evaluate the vasodilatory effect and mechanism of action employed by the crude extract of P. notoginseng. The fingerprint of P. notoginseng was developed using tri-step FTIR and HPTLC. The contents of Rg1 and Rb1 in the active extract (PN95) were further quantified via HPTLC. The vasodilatory effect of PN95 was evaluated using an in vitro aortic ring model. The results showed that PN95 contains a high amount of Rg1 and Rb1, 25.9 and 13.6%, respectively. The vasodilatory effect of PN95 was elicited via the NO/sGC/cGMP and β2-adrenergic receptors pathways. Furthermore, PN95 could manage vascular tone by regulating action potentials via potassium and both VOCC and IP3R pathways. The results obtained fulfilled the expected outcome where the PN95 employed more signaling pathways than any of the single active compounds; hence, the holistic therapeutic effect could be achieved and would more easily translate to applications for the treatment of human diseases.
Chiew Hoong Ng, Ying Chen, Yung Sing Ch’ng, Chu Shan Tan, Zhao Qin Yeap, Yean Chun Loh, Shui-Sheng Wu, and Mun Fei Yam
Elsevier BV
Abstract Gelsemium elegans is a commonly used herb to treat different kinds of diseases. However, the indole alkaloid present in the plant might cause serious side effects. In this research, the infrared spectroscopic identification approach including Fourier transform infrared spectroscopy (FT-IR), Second derivative infrared spectra (SD-IR) and two-dimensional correlation infrared spectra (2D-IR) was used to develop a simple and rapid method to discriminate the stem, leaf and root of the Gelsemium elegans plant. This is because the stem, leaf and root contained different amount of indole alkaloid that contributed to the toxicity. Through this study, all the three parts were successfully identified and discriminated through the infrared spectroscopic identification method. The identification approach was also validated by comparing the samples of the mixture of both stem and root (SR) to the stem and root, respectively and also by comparing different plants with Gelsemium elegans plant. Besides that, all the samples of different parts of the Gelsemium elegans were analyzed with the Principal Component Analysis (PCA) and Soft Independent Modelling of Class Analogy (SIMCA) pattern recognition technique to test and verify the experimental results. The SIMCA model was validated by comparing 70 standard herbs to the model. From the results, macroscopic IR fingerprint method and the classification analysis successfully discriminate not only between Gelsemium elegans samples and standard herbs but also successfully distinguished the three different parts of Gelsemium elegans plant.
Mun Yam, Yean Loh, Chu Tan, Siti Khadijah Adam, Nizar Abdul Manan, and Rusliza Basir
MDPI AG
Pain has been considered as a concept of sensation that we feel as a reaction to the stimulus of our surrounding, putting us in harm’s way and acting as a form of defense mechanism that our body has permanently installed into its system. However, pain leads to a huge chunk of finances within the healthcare system with continuous rehabilitation of patients with adverse pain sensations, which might reduce not only their quality of life but also their productivity at work setting back the pace of our economy. It may not look like a huge deal but factor in pain as an issue for majority of us, it becomes an economical burden. Although pain has been researched into and understood by numerous researches, from its definition, mechanism of action to its inhibition in hopes of finding an absolute solution for victims of pain, the pathways of pain sensation, neurotransmitters involved in producing such a sensation are not comprehensively reviewed. Therefore, this review article aims to put in place a thorough understanding of major pain conditions that we experience—nociceptive, inflammatory and physiologically dysfunction, such as neuropathic pain and its modulation and feedback systems. Moreover, the complete mechanism of conduction is compiled within this article, elucidating understandings from various researches and breakthroughs.
Yung Sing Ch'ng, Yean Chun Loh, Chu Shan Tan, Mariam Ahmad, Mohd. Zaini Asmawi, Wan Maznah Wan Omar, and Mun Fei Yam
Mary Ann Liebert Inc
Abstract The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR ...
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MDPI AG
Hypertension is asymptomatic and a well-known “silent killer”, which can cause various concomitant diseases in human population after years of adherence. Although there are varieties of synthetic antihypertensive drugs available in current market, their relatively low efficacies and major application in only single drug therapy, as well as the undesired chronic adverse effects associated, has drawn the attention of worldwide scientists. According to the trend of antihypertensive drug evolution, the antihypertensive drugs used as primary treatment often change from time-to-time with the purpose of achieving the targeted blood pressure range. One of the major concerns that need to be accounted for here is that the signaling mechanism pathways involved in the vasculature during the vascular tone regulation should be clearly understood during the pharmacological research of antihypertensive drugs, either in vitro or in vivo. There are plenty of articles that discussed the signaling mechanism pathways mediated in vascular tone in isolated fragments instead of a whole comprehensive image. Therefore, the present review aims to summarize previous published vasculature-related studies and provide an overall depiction of each pathway including endothelium-derived relaxing factors, G-protein-coupled, enzyme-linked, and channel-linked receptors that occurred in the microenvironment of vasculature with a full schematic diagram on the ways their signals interact. Furthermore, the crucial vasodilative receptors that should be included in the mechanisms of actions study on vasodilatory effects of test compounds were suggested in the present review as well.
Chu Shan Tan, Yean Chun Loh, Chiew Hoong Ng, Yung Sing Ch’ng, Mohd. Zaini Asmawi, Mariam Ahmad, and Mun Fei Yam
Elsevier BV
Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM. This study was designed to investigate the possible mechanism of actions involved in the vasodilatory activity of ABBT-50 by evaluating its vasodilative effect on isolated Sprague Dawley rats in the presence of absence of various antagonists. When pre-contracted with phenylephrine, relaxation was observed in endothelium intact (EC50=0.027±0.003mg/ml, Rmax=109.8±2.12%) and denuded aortic rings (EC50=0.409±0.073mg/ml, Rmax=63.15±1.78%), as well as in endothelium intact aortic rings pre-contracted with potassium chloride (EC50=32.7±12.16mg/ml, Rmax=34.02±3.82%). Significant decrease in the vasodilative effect of ABBT-50 was observed in the presence of Nω-nitro-l-arginine methyl ester (EC50=0.12±0.021mg/ml, Rmax=75.33±3.28%), 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (EC50=0.463±0.18mg/ml, Rmax=54.48±2.02%), methylene blue (EC50=0.19±0.037mg/ml, Rmax=83.69±3.19%), indomethacin (EC50=0.313±0.046mg/ml, Rmax=71.33±4.12%), atropine (EC50=0.146±0.013mg/ml, Rmax=77.2±3.41%), and 4-aminopyridine (EC50=0.045±0.008mg/ml, Rmax=95.55±2.36%). ABBT-50 was also suppressing Ca2+ release from sarcoplasmic reticulum and inhibiting calcium channels. Vasodilatory effects of ABBT-50 are mediated through NO/sGC/cGMP cascade and PGI2, followed by muscarinic pathways and calcium channels.
Yean Chun Loh, Chu Shan Tan, Yung Sing Ch'ng, Mariam Ahmad, Chiew Hoong Ng, and Mun Fei Yam
Mary Ann Liebert Inc
Hypertension, one of the famous "silent killers" that can attack people at any age, is a current hot topic among scientists due to multiple syndromic behavior and concomitant diseases. The new scientific-based Traditional Chinese Medicine (TCM) formulation approach was used in a previous study by combining five TCM herbs, including Gastrodia elata Bl., Uncaria rhynchophylla (Miq.) Miq. ex Havil., Pueraria thomsonii Benth., Panax notoginseng (Burk.) F.H. Chen, and Alisma orientalis (Sam.) Juzep in optimized ratio (named BPAid). The objective of the present study was to evaluate the mechanism pathways employed by BPAid for vasodilatory effect with the use of an in vitro isolated aortic rings assay. Interestingly, all the mechanisms investigated were involved in the BPAid's vasodilation activity in which the majority contributed through the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) pathways, followed by prostacyclin (PGI2), β2-adrenergic, and M3-receptors pathways. Furthermore, the BPAid appeared to manage vascular tone by regulating action potential through potassium and both voltage-operated calcium channel and inositol triphosphate receptor (IP3R) pathways. The results obtained has confirmed the expected outcome that the benefits of TCM herbs in BPAid can meet the criteria of counteracting multiple signaling mechanism pathways involved in the etiology of hypertension. In addition to this study, the fingerprints and chemical properties of BPAid was identified by using tri-step Fourier transform infrared spectroscopy and compared with its derivatives. The results obtained suggested that the majority of the vasodilatory effects exerted by BPAid were attributed to the presence of saponins and aromatic ring-containing vasoactive compounds.
Yean Chun Loh, Yung Sing Ch'ng, Chu Shan Tan, Mariam Ahmad, Mohd Zaini Asmawi, and Mun Fei Yam
Mary Ann Liebert Inc
Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.
Chu Shan Tan, Yung Sing Ch’ng, Yean Chun Loh, Mohd. Zaini Asmawi, Mariam Ahmad, and Mun Fei Yam
Elsevier BV
ETHNOPHARMACOLOGICAL RELEVANCE
Glycyrrhiza uralensis (G. uralensis) is one of the herbs used in traditional Chinese medicine (TCM) and serves as an envoy medicinal. Since G. uralensis plays a major role in the anti-hypertensive TCM formulae, we believe that G. uralensis might possess vasorelaxation activity.
AIM OF THE STUDY
This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect.
MATERIALS AND METHODS
The vasorelaxation effect of G. uralensis extracts were evaluated on thoracic aortic rings isolated from Sprague Dawley rats.
RESULTS
Among these three extracts of G. uralensis, 50% ethanolic extract (EFG) showed the strongest vasorelaxation activity. EFG caused the relaxation of the aortic rings pre-contracted with phenylephrine either in the presence or absence of endothelium and pre-contracted with potassium chloride in endothelium-intact aortic ring. Nω-nitro-L-arginine methyl ester, methylene blue, or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one inhibit the vasorelaxation effect of EFG in the presence of endothelium. On the other hand, in the presence of the potassium channel blockers (tetraethylammonium and barium chloride), the vasorelaxation effect of EFG was not affected, but glibenclamide and 4-aminopyridine did inhibit the vasorelaxation effect of EFG. With indomethacin, atropine and propranolol, the vasorelaxation effect by EFG was significantly reduced. EFG was also found to be effective in reducing Ca2+ release from sarcoplasmic reticulum and the blocking of calcium channels.
CONCLUSIONS
The results obtained suggest that EFG is involved in the NO/sGC/cGMP pathway.