Overview of Signaling Mechanism Pathways Employed by BPAid in Vasodilatory Activity

Yean Chun Loh,Chu Shan Tan,Yung Sing Ch’ng,Mariam Ahmad,Chiew Hoong Ng,Mun Fei Yam 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.12

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.

Orthogonal Stimulus-Response as a Tool to Formulate Traditional Chinese Medicinal Herbal Combination - New Scientific-Based TCM Herbal Formulating Method –

Yean Chun Loh,Chu Shan Tan,Mun Fei Yam,Chuan Wei Oo,Wan Maznah Wan Omar 대한약침학회 2018 Journal of pharmacopuncture Vol.21 No.3

Objectives: There is an increasing number of complex diseases that are progressively more difficult to be controlled using the conventional “single compound, single target” approach as demonstrated in our current modern drug development. TCM might be the new cornerstone of treatment alternative when the current treatment option is no longer as effective or that we have exhausted it as an option. Orthogonal stimulus-response compatibility group study is one of the most frequently employed formulas to produce optimal herbal combination for treatment of multi-syndromic diseases. This approach could solve the relatively low efficacy single drug therapy usage and chronic adverse effects caused by long terms administration of drugs that has been reported in the field of pharmacology and medicine Methods: The present review was based on the Science Direct database search for those related to the TCM and the development of antihypertensive TCM herbal combination using orthogonal stimulus-response compatibility group studies approach. Results: Recent studies have demonstrated that the orthogonal stimulus-response compatibility group study approach was most frequently used to formulate TCM herbal combination based on the TCM principles upon the selection of herbs, and the resulting formulated TCM formula exhibited desired outcomes in treating one of global concerned complex multi-syndromic diseases, the hypertension. These promising therapeutic effects were claimed to have been attributed by the holistic signaling mechanism pathways employed by the crude combination of herbs. Conclusion: The present review could serve as a guide and prove the feasibility of TCM principles to be used for future pharmacological drug research development.

Vasodilatory Effects of Combined Traditional Chinese Medicinal Herbs in Optimized Ratio

Yean Chun Loh,Chu Shan Tan,Yung Sing Ch’ng,Mariam Ahmad,Mohd. Zaini Asmawi,Mun Fei Yam 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.3

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus–response compatibility group studies by using L25 (55) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed.

Mechanisms of Action of Uncaria rhynchophylla Ethanolic Extract for Its Vasodilatory Effects

Yean Chun Loh,Yung Sing Ch’ng,Chu Shan Tan,Mariam Ahmad,Mohd. Zaini Asmawi,Mun Fei Yam 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.9

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.

Orthogonal Stimulus-Response as a Tool to Formulate Traditional Chinese Medicinal Herbal Combination - New Scientific-Based TCM Herbal Formulating Method -

Loh, Yean Chun,Tan, Chu Shan,Yam, Mun Fei,Oo, Chuan Wei,Omar, Wan Maznah Wan KOREAN PHARMACOPUNCTURE INSTITUTE 2018 Journal of pharmacopuncture Vol.21 No.3

Objectives: There is an increasing number of complex diseases that are progressively more difficult to be controlled using the conventional "single compound, single target" approach as demonstrated in our current modern drug development. TCM might be the new cornerstone of treatment alternative when the current treatment option is no longer as effective or that we have exhausted it as an option. Orthogonal stimulus-response compatibility group study is one of the most frequently employed formulas to produce optimal herbal combination for treatment of multi-syndromic diseases. This approach could solve the relatively low efficacy single drug therapy usage and chronic adverse effects caused by long terms administration of drugs that has been reported in the field of pharmacology and medicine Methods: The present review was based on the Science Direct database search for those related to the TCM and the development of antihypertensive TCM herbal combination using orthogonal stimulus-response compatibility group studies approach. Results: Recent studies have demonstrated that the orthogonal stimulus-response compatibility group study approach was most frequently used to formulate TCM herbal combination based on the TCM principles upon the selection of herbs, and the resulting formulated TCM formula exhibited desired outcomes in treating one of global concerned complex multi-syndromic diseases, the hypertension. These promising therapeutic effects were claimed to have been attributed by the holistic signaling mechanism pathways employed by the crude combination of herbs. Conclusion: The present review could serve as a guide and prove the feasibility of TCM principles to be used for future pharmacological drug research development.

A traditional folk medicine in Malaysia: porcupine bezoar

Chu Shan Tan,Chiew Hoong Ng,Yean Chun Loh,Mun Fei Yam 경희대학교 융합한의과학연구소 2019 Oriental Pharmacy and Experimental Medicine Vol.19 No.2

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.

Vasodilation and Antihypertensive Activities of Swietenia macrophylla (Mahogany) Seed Extract

Yung Sing Ch’ng,Yean Chun Loh,Chu Shan Tan,Mariam Ahmad,Mohd. Zaini Asmawi,Wan Maznah Wan Omar,Mun Fei Yam 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.3

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 macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3′,5′-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.

Impact resistance efficiency of bio-inspired sandwich beam with different arched core materials

Ahmad B.H. Kueh,Chun-Yean Tan,MOHD YAZID YAHYA,Mat Uzir Wahit 국제구조공학회 2022 Steel and Composite Structures, An International J Vol.44 No.1

Impact resistance efficiency of the newly designed sandwich beam with a laterally arched core as bio-inspired by the woodpecker is numerically investigated. The principal components of the beam comprise a dual-core system sandwiched by the top and bottom laminated CFRP skins. Different materials, including hot melt adhesive, high-density polyethylene (HDPE), acrylonitrile butadiene styrene (ABS), epoxy resin (EPON862), aluminum (Al6061), and mild carbon steel (AISI1018), are considered for the side-arched core layer of the beam for impact efficiency assessment. The aluminum honeycomb takes the role of the second core. Contact force, stress, damage formation, and impact energy for beams equipped with different materials are examined. A diversity in performance superiority is noticed in each of these indicators for different core materials. Therefore, for overall performance appraisal, the impact resistance efficiency index, which covers several chief impact performance parameters, of each sandwich beam is computed and compared. The impact resistance efficiency index of the structure equipped with the AISI1018 core is found to be the highest, about 3-10 times greater than other specimens, thus demonstrating its efficacy as the optimal material for the bio-inspired dual-core sandwich beam system.

Vasorelaxation Study and Tri-Step Infrared Spectroscopy Analysis of Malaysian Local Herbs

Ch'ng, Yung Sing,Tan, Chu Shan,Loh, Yean Chun,Ahmad, Mariam,Asmawi, Mohd. Zaini,Yam, Mun Fei KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.2

Objectives: The aim of this paper is to investigate the activities of Malaysian local herbs (Clinacanthus nutans Lindau, Strobilanthes crispus, Murdannia bracteata, Elephantopus scaber Linn., Pereskia bleo, Pereskia grandifolia Haw., Vernonia amygdalina, and Swietenia macrophylla King) for anti-hypertensive and vasorelaxant activity. An infrared (IR) macro-fingerprinting technique consisting of conventional fourier transform IR (FTIR), second-derivative IR (SD-IR), and two-dimensional correlation IR (2D-correlation IR) analyses were used to determine the main constituents and the fingerprints of the Malaysian local herbs. Methods: The herbs were collected, ground into powder form, and then macerated by using three different solvents: distilled water, 50% ethanol, and 95% ethanol, respectively. The potentials of the extracts produced from these herbs for use as vasorelaxants were determined. Additionally, the fingerprints of these herbs were analyzed by using FTIR spectra, SD-IR spectra, and 2D-correlation IR spectra in order to identify their main constituents and to provide useful information for future pharmacodynamics studies. Results: Swietenia macrophylla King has the highest potential in terms of vasorelaxant activity, followed by Vernonia amygdalina, Pereskia bleo, Strobilanthes crispus, Elephantopus scaber Linn., Pereskia grandifolia Haw., Clinacanthus nutans Lindau, and Murdannia bracteata. The tri-step IR macro-fingerprint of the herbs revealed that most of them contained proteins. Pereskia bleo and Pereskia grandifolia Haw. were found to contain calcium oxalate while Swietenia macrophylla King was found to contain large amounts of flavonoids. Conclusion: The flavonoid content of the herbs affects their vasorelaxant activity, and the tri-step IR macro-fingerprint method can be used as an analytical tool to determine the activity of a herbal medicine in terms of its vasorelaxant effect.

Vasorelaxation Study and Tri-Step Infrared Spectroscopy Analysis of Malaysian Local Herbs

Yung Sing Ch’ng,Chu Shan Tan,Yean Chun Loh,Mariam Ahmad,Mohd. Zaini Asmawi,Mun Fei Yam 대한약침학회 2016 Journal of pharmacopuncture Vol.19 No.2

Objectives: The aim of this paper is to investigate the activities of Malaysian local herbs (Clinacanthus nutans Lindau, Strobilanthes crispus, Murdannia bracteata, Elephantopus scaber Linn., Pereskia bleo, Pereskia grandifolia Haw., Vernonia amygdalina, and Swietenia macrophylla King) for anti-hypertensive and vasorelaxant activity. An infrared (IR) macro-fingerprinting technique consisting of conventional fourier transform IR (FTIR), second-derivative IR (SD-IR), and two-dimensional correlation IR (2D-correlation IR) analyses were used to determine the main constituents and the fingerprints of the Malaysian local herbs. Methods: The herbs were collected, ground into powder form, and then macerated by using three different solvents: distilled water, 50% ethanol, and 95% ethanol, respectively. The potentials of the extracts produced from these herbs for use as vasorelaxants were determined. Additionally, the fingerprints of these herbs were analyzed by using FTIR spectra, SD-IR spectra, and 2D-correlation IR spectra in order to identify their main constituents and to provide useful information for future pharmacodynamics studies. Results: Swietenia macrophylla King has the highest potential in terms of vasorelaxant activity, followed by Vernonia amygdalina, Pereskia bleo, Strobilanthes crispus, Elephantopus scaber Linn., Pereskia grandifolia Haw.,Clinacanthus nutans Lindau, and Murdannia bracteata. The tri-step IR macro-fingerprint of the herbs revealed that most of them contained proteins. Pereskia bleo and Pereskia grandifolia Haw. were found to contain calcium oxalate while Swietenia macrophylla King was found to contain large amounts of flavonoids. Conclusion: The flavonoid content of the herbs affects their vasorelaxant activity, and the tri-step IR macro- fingerprint method can be used as an analytical tool to determine the activity of a herbal medicine in terms of its vasorelaxant effect.