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Hesperetin is one of the prominent flavonoids found in citrus fruit. Several research studies have reported that hesperetin can promote vasodilation in vascular tissue by increasing the level of nitric oxide and cyclic nucleotides. However, these may not be the only pathway for hesperetin to exert its vasodilatory effect. In addition to vasodilation, hesperetin has been found to carry an antihypertensive effect through intraperitoneal injection, although no study has comprehensively investigated the antihypertensive effect of hesperetin through oral administration. Therefore, this study aimed to determine the possible mechanism pathways involved in hesperetin-induced vasodilation and investigated its antihypertensive effects on hypertensive rats' model via oral administration. The ex vivo experimental findings showed that the NO/sGC/cGMP signalling pathway was involved in hesperetin-mediated vasodilation. Moreover, hesperetin activated the AC/cAMP/PKA pathway through PGI2 and activated the ß2-adrenergic receptor. Hesperetin can act as a voltage-gated potassium channel (KV) and ATP-sensitive potassium channel (KATP) opener. The intracellular calcium in vascular smooth muscle was reduced by hesperetin through blocking the voltage-operated calcium channels (VOCC) and inositol triphosphate receptor (IP3R). In the in vivo assessment, hesperetin shows a significant decrease in Spontaneously Hypertensive rats' blood pressure following 21 days of oral treatment. The sub-chronic toxicity assessment demonstrated that hesperetin exhibited no deleterious effects on the body weights, clinical biochemistry and haematological profile of Sprague-Dawley rats. This study implies that hesperetin holds promise as a potential medication for hypertension treatment, devoid of undesirable side effects.
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Rationale: Ganoderma lucidum (G. lucidum) is a popular medicinal fungus that has been used in traditional medicine for decades, with its provenance influencing its medicinal and commercial worth. The amount of active ingredients and the price of G. lucidum from different origins vary significantly; hence, fraudulent labeling is common. Reliable techniques for G. lucidum geographic verification are urgently required to safeguard the interests of consumers, producers, and honest dealers. A stable isotope is widely acknowledged as a useful traceability technique and could be developed to confirm the geographical origin of G. lucidum. Methods: G. lucidum samples from various sources and in varying stages were identified by using δ 13C, δD, δ 18O, δ 15N, C, and N contents combined with chemometric tools. Chemometric approaches, including PCA, OPLS-DA, PLS, and FLDA models, were applied to the obtained data. The established models were used to trace the origin of G. lucidum from various sources or track various stages of G. lucidum. Results: In the stage model, the δ 13C, δD, δ 18O, δ 15N, C, and N contents were considered meaningful variables to identify various stages of G. lucidum (bud development, growth, and maturing) using PCA and OPLS-DA and the findings were validated by the PLS model rather than by only four variables (δ 13C, δD, δ 18O, and δ 15N). In the origin model, only four variables, namely δ 13C, δD, δ 18O, and δ 15N, were used. PCA divided G. lucidum samples into four clusters: A (Zhejiang), B (Anhui), C (Jilin), and D (Fujian). The OPLS-DA model could be used to classify the origin of G. lucidum. The model was validated by other test samples (Pseudostellaria heterophylla), and the external test (G. lucidum) by PLS and FLDA models demonstrated external verification accuracy of up to 100%. Conclusion: C, H, O, and N stable isotopes and C and N contents combined with chemometric techniques demonstrated considerable potential in the geographic authentication of G. lucidum, providing a promising method to identify stages of G. lucidum.
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Dioscorea oppositifolia is an important crop and functional food. D. oppositifolia tuber is often adulterated with D. persimilis, D. alata, and D. fordii tuber in the commercial market. This study proposed an integrated Fourier transform infrared spectroscopy (FT-IR) with chemometric approach to differentiate these four Dioscorea species. A total of 107 Dioscorea spp. tuber samples were collected from different locations in China. Principal Component Analysis (PCA), PCA-Class, and Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) were utilised to classify the FT-IR spectra. In this PCA is unable to differentiate the Dioscorea spp. tuber effectively. However, PCA-Class and OPLS-DA can distinguish spp. these 4 species Dioscorea tuber with high accuracy, sensitivity, and specificity. Additionally, the RMSEE, RMSEP and RMSECV values for OPLS-DA model were low, showing that it is a good model. The combination of FT-IR with the PCA-Class and OPLS-DA is practical in discriminating Dioscorea spp. tubers.
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Dioscorea , Quimiometría , Espectroscopía Infrarroja por Transformada de Fourier , China , Análisis DiscriminanteRESUMEN
Introduction: Taxus species are used as medicinal plants all over the world. The leaves of Taxus species are sustainable medicinal resources that are rich in taxoids and flavonoids. However, traditional identification methods cannot effectively identify Taxus species on the basis of leaces used as raw medicinal materials, because their appearance and morphological characteristics are almost the same, and the probability of error identification increases in accordance with the subjective consciousness of the experimenter. Moreover, although the leaves of different Taxus species have been widely used, their chemical components are similar and lack systematic comparative research. Such a situation is challenging for quality assessment. Materials and methods: In this study, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with chemometrics was applied for the simultaneous determination of eight taxoids, four flavanols, five flavonols, two dihydroflavones, and five biflavones in the leaves of six Taxus species, namely, T. mairei, T. chinensis, T. yunnanensis, T. wallichiana, T. cuspidata, and T. media. Chemometric methods, including hierarchical cluster analysis, principal component analysis, orthogonal partial least squares-discriminate analysis, random forest iterative modeling, and fisher linear discriminant analysis, were utilized to differentiate and evaluate the six Taxus species. Results: This proposed method exhibited good linearity (R 2 = 0.9999-0.9972) with a lower quantification limits of 0.94-3.05 ng/mL for all analytes. The intra- and inter-day precisions were within 6.83%. Six compounds, namely, 7-xylosyl-10-deacetyltaxol, ginkgetin, rutin, aromadendrin, 10-deacetyl baccatin III, and epigallocatechin, were identified through chemometrics for the first time. These compounds can be used as important chemical markers to distinguish the above six Taxus species rapidly. Conclusion: This study established a method for determination of the leaves of six Taxus species, and revealing the differences in the chemical components of these six Taxus species.
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Chrysin, a bioflavonoid belonging to the flavone, occurs naturally in plants such as the passionflower, honey and propolis. Few studies have demonstrated that chrysin can promote vasorelaxant activities in rats' aorta and mesenteric arteries. To date, no research has explored the signalling system routes that chrysin may utilise to produce its vasorelaxant action. Therefore, this study aimed to investigate the underlying mechanisms involved in chrysin-induced vasorelaxant in rats' aortic rings and assess the antihypertensive effect of chrysin in spontaneously hypertensive rats (SHRs). The findings revealed that chrysin utilised both endothelium-dependent and endothelium-independent mechanisms. The presence of L-NAME (endothelial NO synthase inhibitor), ODQ (sGC inhibitor), methylene blue (cGMP lowering agent), 4-AP (voltage-gated potassium channel inhibitor), atropine (muscarinic receptors inhibitor) and propranolol (ß-adrenergic receptors inhibitor) significantly reduced the chrysin's vasorelaxant action. Furthermore, chrysin can reduce intracellular Ca2+ levels by limiting the extracellular intake of Ca2+ through voltage-operated calcium channels and blocking the intracellular release of Ca2+ from the sarcoplasmic reticulum via the IP3 receptor. These indicate that chrysin-induced vasorelaxants involved NO/sGC/cGMP signalling cascade, muscarinic and ß-adrenergic receptors, also the potassium and calcium channels. Although chrysin had vasorelaxant effects in in vitro studies, the in vivo antihypertensive experiment discovered chrysin does not significantly reduce the blood pressure of SHRs following 21 days of oral treatment. This study proved that chrysin utilised multiple signalling pathways to produce its vasorelaxant effect in the thoracic aorta of rats; however, it had no antihypertensive effect on SHRs.
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Antihipertensivos , Vasodilatación , Animales , Ratas , Antihipertensivos/farmacología , Antihipertensivos/metabolismo , Aorta Torácica , Canales de Calcio/metabolismo , GMP Cíclico/metabolismo , Endotelio Vascular , Ratas Endogámicas SHR , Receptores Adrenérgicos beta/metabolismo , Vasodilatadores/farmacologíaRESUMEN
Camellia nitidissima C.W. Chi is a golden camellia recognized in Chinese herbology and widely used as tea and essential oil in Chinese communities. Due to its diverse pharmacological properties, it can be used to treat various diseases. However, unethical sellers adulterated the flower with other parts of Camellia nitidissima in their product. This study used an integrated tri-step infrared spectroscopy method and a chemometric approach to distinguish C. nitidissima's flowers, leaves, and seeds. The three different parts of C. nitidissima were well distinguished using Fourier transform infrared spectroscopy (FT-IR), second-derivative infrared (SD-IR) spectra, and two-dimensional correlation infrared (2D-IR) spectra. The FT-IR and SD-IR spectra of the samples were subjected to principal component analysis (PCA), PCA-class, and orthogonal partial least square discriminant analysis (OPLS-DA) for classification and discrimination studies. The three parts of C. nitidissima were well separated and discriminated by PCA and OPLS-DA. The PCA-class model's sensitivity, accuracy, and specificity were all >94%, indicating that PCA-class is the good model. In addition, the RMSEE, RMSEP, and RMSECV values for the OPLS-DA model were low, and the model's sensitivity, accuracy, and specificity were all 100%, showing that it is the excellent one. In addition, PCA-class and OPLS-DA obtained scores of 27/32 and 26/32, respectively, for detecting adulterated and other TCM reference flower samples from C. nitidissima. Combining an infrared spectroscopic method with a chemometric approach proved that it is possible to differentiate distinct sections of C. nitidissima and discriminate adulterated samples of C.nitidissima flower.
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4-hydroxybenzaldehyde (4HB), known as ρ-hydroxybenzaldehyde, is commonly present in traditional Chinese medicine herb, most frequently used for hypertension treatment. This research aims to determine the potency of 4HB's vasorelaxant action. In the study, the vasodilation effect of 4HB was evaluated using in vitro isolated rat aortic rings assay. The aortic rings were pre-incubated with respective antagonists before being pre-contracted with phenylephrine (PE) and challenged with various concentrations of 4HB for mechanistic action studies. Rmax (maximal vasodilation) and pEC50 (negative logarithm of half-maximal effective concentration) values of each experiment were determined for comparison purposes. 4HB caused vasodilation on endothelium-intact aortic rings which pre-contracted with PE (pEC50 = 3.53 ± 0.05, Rmax = 100.95 ± 4.25%) or potassium chloride (pEC50 = 2.96 ± 0.13, Rmax = 72.13 ± 4.93%). The vasodilation effect of 4HB was significantly decreased in the absence of an endothelium (pEC50 = 2.21 ± 0.25, Rmax = 47.96 ± 4.16%). The atropine, 4-aminopyridine, Nω-nitro-L-arginine methyl ester, glibenclamide, and propranolol significantly reduced the vasorelaxation effect of 4HB. Besides that, 4HB blocked the voltage-operated calcium channel (VOCC) and regulated the intracellular Ca2+ release from the sarcoplasmic reticulum (SR) in the aortic ring. Thus, the results indicated that 4HB exerted its vasodilatory effect via cGMP and ß2 pathways, M3-dependent PLC/IP3 pathways, and potassium and calcium channels.
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Factores Relajantes Endotelio-Dependientes , Vasodilatación , Animales , Aorta Torácica , Benzaldehídos , Calcio/metabolismo , Canales de Calcio/metabolismo , Endotelio , Endotelio Vascular , Factores Relajantes Endotelio-Dependientes/metabolismo , Factores Relajantes Endotelio-Dependientes/farmacología , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta/metabolismo , Vasodilatadores/farmacologíaRESUMEN
A proof-of-concept medicinal herbs identification scheme using machine learning classifiers is proposed in the form of an automated computational package. The scheme makes use of two-dimensional correlation Fourier Transformed Infrared (FTIR) fingerprinting maps derived from the FTIR of raw herb spectra as digital input. The prototype package admits a collection of 11 machine learning classifiers to form a voting pool. A common set of oversampled dataset containing 5 different herbal classes is used to train the pool of classifiers on a one-verses-others manner. The collections of trained models, dubbed the voting classifiers, are deployed in a collective manner to cast their votes to support or against a given inference fingerprint whether it belongs to a particular class. By collecting the votes casted by all voting classifiers, a logically designed scoring system will select out the most probable guess of the identity of the inference fingerprint. The same scoring system is also capable of discriminating an inference fingerprint that does not belong to any of the classes the voting classifiers are trained for as the 'others' type. The proposed classification scheme is stress-tested to evaluate its performance and expected consistency. Our experimental runs show that, by and large, a satisfactory performance of the classification scheme of up to 90 % accuracy is achieved, providing a proof-of-concept viability that the proposed scheme is a feasible, practical, and convenient tool for herbal classification. The scheme is implemented in the form of a packaged Python code, dubbed the "Collective Voting" (CV) package, which is easily scalable, maintained and used in practice.
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Plantas Medicinales , Algoritmos , Aprendizaje Automático , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
PURPOSE: To evaluate therapeutic effectiveness of antibacterial triclosan (TCS) and anti-inflammatory flurbiprofen (FLB)-loaded nanogels system in ligature-induced experimental periodontitis in rats. METHODOLOGY: A total of 72 Sprague-Dawley rats were used in this study. Four groups (n = 18 each) were randomly created: Group 1 - neither subjected to experimental periodontitis nor to any treatment; Group 2 - subjected to experimental periodontitis but not treated; Group 3 - subjected to experimental periodontitis and then treated with the developed nanogels; Group 4 - subjected to experimental periodontitis and then placed on a mixture of pure TCS and FLB treatment. The experimental periodontitis was induced on the lower incisors by applying a ligature which was kept for 14 days. Treatment was done for 7 days, and sampling was done at 7, 14, and 28 day of the post-induction experimental period. Morphometric analysis was conducted to assess the clinical outcomes and healing effect. RESULTS: The morphometric findings showed that the group treated with the developed TCS and FLB-loaded nanogels recovered better and faster than a mixture of pure TCS and FLB. At 28 day of the experimental period, there was no significant difference (p > 0.05) between the baseline control group and the nanogels treated group. CONCLUSIONS: The developed TCS and FLB-loaded nanogels was found to be effective in the treatment of experimental periodontitis in rats. The used experimental periodontitis model was found to be simple and easily reproducible.
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Naringenin is a naturally occurring flavanone (flavonoid) known to have bioactive effects on human health. It has been reported to show cardiovascular effects. This study aimed to investigate the possible vasorelaxant effect of naringenin and the mechanism behind it by using a Sprague Dawley rat aortic ring assay model. Naringenin caused significant vasorelaxation of endothelium-intact aortic rings precontracted with phenylephrine (pD2 = 4.27 ± 0.05; Rmax = 121.70 ± 4.04%) or potassium chloride (pD2 = 4.00 ± 0.04; Rmax = 103.40 ± 3.82%). The vasorelaxant effect decreased in the absence of an endothelium (pD2 = 3.34 ± 0.10; Rmax = 62.29 ± 2.73%). The mechanisms of the vasorelaxant effect of naringenin in the presence of antagonists were also investigated. Indomethacin, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, atropine, 4-aminopyridine, Nω-nitro-l-arginine methyl ester, glibenclamide and propranolol significantly reduced the relaxation stimulated by naringenin in the presence of endothelium. Besides that, the effect of naringenin on the voltage-operated calcium channel (VOCC) in the endothelium-intact aortic ring was studied, as was intracellular Ca2+ release from the sarcoplasmic reticulum (SR) in the endothelium-denuded aortic ring. The results showed that naringenin also significantly blocked the entry of Ca2+ via the VOCC, SERCA/SOCC and suppressed the release of Ca2+ from the SR. Thus, the vasorelaxant effect shown by naringenin mostly involve the COX pathway, the endothelium-dependent pathway via NO/sGC/prostaglandin, calcium and potassium channels.
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Aorta Torácica/efectos de los fármacos , Canales de Calcio/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Flavanonas/farmacología , Canales de Potasio/metabolismo , Vasodilatadores/farmacología , Animales , Aorta Torácica/citología , Aorta Torácica/metabolismo , Aorta Torácica/fisiología , Relación Dosis-Respuesta a Droga , Ratas , Ratas Sprague-DawleyRESUMEN
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 ß2-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.
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Antihipertensivos/farmacología , Aorta/efectos de los fármacos , Estilbenos/farmacología , Vasodilatadores/farmacología , Animales , Antihipertensivos/química , Aorta/fisiopatología , Descubrimiento de Drogas , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Ratas Sprague-Dawley , Estilbenos/química , Vasodilatación/efectos de los fármacos , Vasodilatadores/químicaRESUMEN
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.
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Antihipertensivos/farmacología , Aorta Torácica/efectos de los fármacos , Vasos Sanguíneos/efectos de los fármacos , Descubrimiento de Drogas , Estilbenos/farmacología , Vasodilatadores/farmacología , Animales , Antihipertensivos/síntesis química , Antihipertensivos/química , Relación Dosis-Respuesta a Droga , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Estilbenos/síntesis química , Estilbenos/química , Relación Estructura-Actividad , Vasodilatadores/síntesis química , Vasodilatadores/químicaRESUMEN
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, 1 H and 13 C 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.
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In this study, the bioactivity-guided fractionation was conducted on the aerial parts of Arctium lappa L. and then the extracts were tested in vitro on breast cancer (MCF-7), colorectal cancer (HCT-116), and normal cells (EA.hy926). The n-hexane fraction (EHX) of the ethanolic extract showed strong activity against both MCF-7 and EA.hy926 cell lines (IC50 values: 14.08 ± 3.64 and 27.25 ± 3.45 µg/mL, respectively). The proapoptotic activity of EHX was assessed using MCF-7. Morphological alterations were visualized using Hoechst staining and a transmission electron microscope. Cancer cell signal transduction pathways were investigated, and EHX significantly upregulated p53, TGF-ß, and NF-κB. Furthermore, EHX was found to disrupt the metastatic cascade of breast cancer cells by the inhibition of cell proliferation, migration, invasion, and colonization. The antiangiogenic activity of EHX fraction showed potent inhibition of rat aorta microvessels with IC50 value: 4.34 ± 1.64 µg/mL. This result was supported by the downregulation of VEGF-A expression up to 54%. Over 20 compounds were identified in EHX using GC-MS, of which stigmasterol, ß-sitosterol, and 3-O-acetyllupeol are the major active compounds. Phytochemical analysis of EHX showed higher phenolic and flavonoid contents with a substantial antioxidant activity. In conclusion, this work demonstrated that A. lappa has valuable anticancer activity and antiangiogenic properties that might be useful in breast cancer therapy.
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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.
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Analgésicos/uso terapéutico , Dolor/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Dolor/etiología , Dimensión del Dolor , Transducción de SeñalRESUMEN
Morin (3,5,7,2',4'-pentahydroxyflavone) is a yellow coloured natural flavonoid found in plants of the Moraceae family. This favonoid is easily sources from readily available fruits, vegetables and eve certain beverages. Among the sources that was identified, it is clear that morin is most abundantly found in almond, old fustic, Indian guava, and Osage orange. Multiple studies have suggested that morin has multiple therapeutic actions and possess potential to be a functional potent drug. Previous studies demonstrated that morin is capable of resolving deoxycorticosterone acetate-salt-induced hypertension and possess strong vasorelaxant properties. However, the exact mechanisms remains unknown. Therefore, this study is designed to investigate the in vitro mechanism of morin-induced vasorelaxant effects. The underlying mechanisms of morin's vasorelaxant activities were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats. Results from the study demonstrated morin causing vasodilatory reaction in phenylephrine and potassium chloride pre-contracted endothelium-intact aortic rings with the effect being significantly affected in endothelium-denuded aortic rings. Pre-incubation of the aortic rings with ODQ (selective cGMP-independent sGC inhibitor), indomethacin (nonselective COX inhibitor), L-NAME (endothelial nitric oxide inhibitor), propranolol (ß2-adrenegic receptors blocker), and atropine (muscarinic receptors blocker) significantly reduced the vasorelaxant effect of morin. It was also found to be able to reduce the intracellular calcium level by blocking VOCC and calcium intake from the extracellular environment and the intracellular release of calcium from the sarcoplasmic reticulum. The present study showed that the vasorelaxant effect of morin potentially involves the NO/sGC, muscarinic receptors, ß2-adrenegic receptors, and calcium channels.