Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Effects of Maturation on Antibacterial Properties of Vietnamese Mango (Mangifera indica) Leaves.

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents.

Habu snakes (Protobothrops flavoviridis) show variation in thoracic aortic vasoreactivity between adjacent Japanese islands.

Habu snakes (Protobothrops flavoviridis) are pit vipers found in the geographically adjacent but ecologically divergent islands of Tokunoshima and Amami-Oshima in southwestern Japan. Abiotic factors can cause variation in animal populations between the two islands, and Habu snakes may show such intraspecific physiological variation. We therefore evaluated the vasoreactivity in aortas isolated from the Habu of both islands. Tokunoshima Habu showed significantly greater contractile responses to angiotensin (Ang) II, acetylcholine (ACh) and noradrenaline, and significantly higher affinities (pEC50) for Ang II and ACh, than Amami-Oshima Habu. ACh caused contractions in aortas from both populations, a finding previously unreported in snakes. Our findings indicate that vasoreactivity may differ between Tokunoshima and Amami-Oshima Habu.

Characterization of Vasoreactivity in a Semi-Arboreal Snake, the Tokara Habu (Protobothrops tokarensis).

Vasoreactivity is relatively well documented in terrestrial snakes but has previously been investigated in only one semi-arboreal snake species. Consequently, the extent to which vasoreactivity is common across snake taxa or varies by habitat is unclear. The Tokara habu (Protobothrops tokarensis) is a semi-arboreal snake endemic to only two small adjacent Japanese islands, and hence a useful species for further investigation of vasoreactivity. We evaluated responses to known vasoactive substances in thoracic aortas isolated from Tokara habu. Under resting tension, noradrenaline and angiotensin II induced concentration-dependent contraction, but acetylcholine, serotonin (5-hydroxytriptamine; 5-HT), and isoproterenol induced relaxation followed by contraction. Histamine and rattlesnake bradykinin had no effect. Experiments with receptor-specific antagonists suggest that M1 and M3 receptors are involved in the acetylcholine-induced response; 5-HT1, 5-HT2, and 5-HT7 receptors in the serotonin-induced response; and ß1 and ß2 adrenoceptors in isoproterenol-induced relaxation. This is the first report on such response patterns in snakes (including serotonin- and isoproterenol-induced relaxation). Nitric oxide may be involved in acetylcholine-induced relaxation but not in the responses to serotonin or isoproterenol. In contrast to the uniform vasoreactivity observed in terrestrial snakes, the vasoreactivity of semi-arboreal snakes may be governed by diverse regulatory mechanisms.

Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

Reduced Nitric Oxide Synthase Involvement in Aigamo Duck Basilar Arterial Relaxation.

The basilar arterial endothelium mediates blood vessel relaxation partly through the release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to a high mortality rate in chickens infected with the highly pathogenic avian influenza virus, but interestingly, ducks exhibit a greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated with 5-HT1 and H1 receptors, while relaxation is induced with ß3-adrenergic and M3 receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated with M3 and OK receptors but not ß3-adrenergic receptors in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain the differences in lethality between ducks and chickens when vascular endothelial cells are infected with the virus.

Short communication: Antibacterial effects of essential oils from Cinnamomum cassia bark and Eucalyptus globulus leaves-The involvements of major constituents.

Essential oils from Cinnamomum cassia bark and Eucalyptus globulus leaves have been traditionally applied for bacterial infections, through both of aromatherapy and oral application. (E)-cinnamaldehyde and 1,8 cineole have been identified as their major secondary metabolites, and are also generally considered as the main active ingredients responsible for their medicinal applications. However, ethnobotanical doctors still prefer to use whole essentials oils over purified compounds in bacterial infections. We therefore hypothesized that multi-compound extracts might exert better effects than isolated ingredients. In order to verify the hypothesis about advantages of whole materials, we examined antibacterial properties of the 2 plant essential oils in the comparison with their isolated major compounds, such as (E)-cinnamaldehyde and 1,8 cineole. Effects of liquid- and vapor-phase were examined on a set of 6 gram-positive and -negative bacteria, applying broth dilution, agar well diffusion and disc volatilization methods. In all 3 investigations, we observed that whole cinnamon and eucalyptus oils, with the lower concentrations of (E)-cinnamaldehyde (89.1%) and 1,8 cineole (61.2%), were able to induce better effects than the purified active compounds (≥ 99%). These results partly explain the advantages of using whole essential oils over isolated ingredients, and therefore support the application of traditional dosage forms for bacterial infections in ethnomedicine.

Strengthening Addiction Care Continuum Through Community Consortium in Vietnam: Protocol for a Cluster-Randomized Controlled Trial.

BACKGROUND: A chronic condition, drug addiction, requires long-term multipronged health care and treatment services. Community-based approaches can offer the advantages of managing integrated care along the care continuum and improving clinical outcomes. However, scant rigorous research focuses on sustainable, community-based care and service delivery. OBJECTIVE: This protocol describes a study aiming to develop and test an intervention that features the alliance of community health workers and family members to provide integrated support and individualized services and treatment for people who use drugs (PWUD) in community settings. METHODS: Based on the National Institute on Drug Abuse's Seek-Test-Treat-Retain (STTR) framework, an intervention that provides training to community health workers will be developed and piloted before an intervention trial. Trained community health workers will conduct home visits and provide support for PWUD and their families. The intervention trial will be conducted in 3 regions in Vietnam, with 60 communities (named communes). These communes will be randomized to either an intervention or control condition. Intervention outcomes will be evaluated at baseline and at 3, 6, 9, and 12 months. The primary outcome measure is PWUD's STTR fulfillment, consisting of multiple individual fulfillment indicators across 5 domains: Seek, Test, Treat, Retain, and Health. The secondary outcomes of interest are the community health workers' service provision and family members' support. The primary analysis will follow an intention-to-treat approach. Generalized mixed-effects regression models will be used to compare changes in the outcome measures from baseline between intervention and control conditions. RESULTS: During the first year of the project, we conducted formative studies, including in-depth interviews and focus groups, to identify service barriers and intervention strategies. The intervention and assessment pilots are scheduled in 2023 before commencing the trial. Reports based on the baseline data will be distributed in early 2024. The intervention outcome results will be available within 6 months of the final data collection date, that is, the main study findings are expected to be available in early 2026. CONCLUSIONS: This study will inform the establishment of community health workers and family members alliance, a locally available infrastructure, to support addiction services and care for PWUD. The methodology, findings, and lessons learned are expected to shed light on the addiction service continuum's implementation and demonstrate a community-based addiction service delivery model that can be transferable to other countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05315492; https://clinicaltrials.gov/ct2/show/NCT05315492. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44219.

Endothelium-independent and calcium channel-dependent relaxation of the porcine cerebral artery by different species and strains of turmeric.

OBJECTIVE: To clarify the underlying mechanism of turmeric, which is traditionally used as a medicinal plant for the treatment of cardiovascular disorders, such as hypertension, and palpitations. METHODS: Methanol extracts of different turmeric were used. A tissue-organ-bath system was used to investigate the vasoactive effects of methanol extracts from 5 kinds of turmeric on isolated porcine basilar arteries. The arterial rings were suspended in physiological solution that was maintained at 37 °C temperature with a continuous supply of 95% O2 and 5% CO2. RESULTS: All turmeric extracts (20-800 µg/mL) induced concentration-dependent relaxation of the isolated porcine basilar artery pre-contracted with U46619 (1-5 × 10-9 M) in arterial rings with or without endothelium. There were no significant differences in the relaxation induced by different turmeric or between the endothelium-intact and denuded arteries. In depolarized, Ca2+-free medium, the turmeric extracts inhibited CaCl2-induced contractions and caused a concentration-dependent rightward shift of the response curves. In addition, propranolol (a non-specific ß-adrenoceptor antagonist) slightly inhibited the relaxation induced by turmeric. In contrast, Nω-nitro-l-arginine, indomethacin, tetraethylammonium, glibenclamide and 4-aminopyridine did not affect turmeric-induced relaxation. CONCLUSION: These results demonstrated that turmeric induced endothelium-independent relaxation of the porcine basilar artery, which may be due to the inhibition of extracellular and intracellular Ca2+ receptors and the partial inhibition of ß-adrenergic receptors in vascular smooth muscle cells.

Antagonistic Effects of Gingko biloba and Sophora japonica on Cerebral Vasoconstriction in Response to Histamine, 5-Hydroxytryptamine, U46619 and Bradykinin.

The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca[Formula: see text], histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9[Formula: see text],11[Formula: see text]-methanoepoxy prostaglandin (PG) F[Formula: see text](U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm. Isolated porcine basilar arteries (PBA) and endothelial cells from them were used as the study materials. Neither SJ nor GB had any effect on the contractions induced by KCl and extracellular Ca[Formula: see text]. SJ significantly inhibited the contraction induced by histamine, 5-HT, U46619 and BK, whereas GB inhibited histamine-induced contraction, but had no effects on the contractions induced by 5-HT, U46619 and BK. In the presence of diphenhydramine (a H1 receptor antagonist), ketanserin (a 5-HT2 receptor antagonist) and ONO-3708 (a thromboxane (TX) A2/PG receptor antagonist), the inhibitory effects of these extracts on the contractions induced by histamine, 5-HT and U46619 were abolished. SJ significantly inhibited the contractions induced by BK and PGF[Formula: see text], but in the presence of ONO-3708 (10[Formula: see text] M) had no effect on them. BK enhanced the production of PGF[Formula: see text] from cultured PBA endothelium cells, and SJ significantly attenuated this enhancement. These results suggest that SJ and GB have a H1-antagonistic effect, and that SJ also attenuates cerebral vasoconstriction mediated via 5-HT2 and TXA2/PG receptors. These findings appear to explain why SJ has been used traditionally as a therapeutic medication for cerebral vasospasm after cerebral hemorrhage.

Pharmacological characteristics of Artemisia vulgaris L. in isolated porcine basilar artery.

ETHNOPHARMACOLOGICAL RELEVANCE: In Vietnamese traditional herbalism, there are conflicting opinions about the effect of Artemisia vulgaris L. (AVL, English name: mugwort) on hypertension. Some ethnic doctors recommend the use of AVL for treatment of hypertension, whereas others advise against it. The purpose of this study was to clarify the pharmacological characteristics of AVL in isolated arteries to explain the conflicts surrounding the use of AVL for treatment of hypertension. MATERIALS AND METHODS: We initially performed a functional study using an organ bath system to investigate the effect of AVL extract on isolated porcine basilar artery. We then measured the change in intracellular free Ca(2+) concentration elicited by AVL using cultured smooth muscle cells loaded with the Ca(2+) indicator fluo-4. Finally, using HPLC, we determined the active components in AVL. RESULTS AND DISCUSSION: AVL induced vasoconstriction at resting tension, and endothelial removal enhanced this effect significantly. Pretreatment with PD123319 (an AT2 receptor antagonist), Nω-nitro-L-arginine (a nitric oxide synthase inhibitor), or both, also enhanced this effect. AVL-induced contraction was competitively inhibited by methiothepin (a 5-HT1 and 5-HT2 receptor antagonist) in the presence of ketanserin (a 5-HT2 receptor antagonist). Removal of extracellular calcium with nifedipine (an L-type Ca(2+) channel blocker) or ruthenium red (a ryanodine receptor blocker) significantly reduced AVL-induced contraction, whereas losartan (an AT1 receptor antagonist) and diphenhydramine (a H1 receptor antagonist) had no effect on this contraction. AVL increased the intracellular free Ca(2+) concentration in cultured cells, and this increment was inhibited by methiothepin. HPLC analysis revealed that the retention time of the first peak in the AVL profile was similar to that of the 5-HT standard, and that addition of 5-HT to the AVL sample enhanced this peak. On the other hand, AVL induced endothelium-independent relaxation under precontracted conditions with 60mM KCl. Captopril (an angiotensin converting enzyme inhibitor), atenolol (a ß1 receptor antagonist) and cimetidine (a H2 receptor antagonist) had no effect on this relaxation. In Ca(2+)-free 60mM KCl-containing solution, pretreatment with AVL significantly inhibited CaCl2-induced contraction. CONCLUSION: For the first time, the present study has demonstrated that AVL has two opposite effects, contraction and relaxation, on isolated artery, which may help to explain the conflicting indications for AVL in traditional herbalism. 5-HT is a significant factor affecting artery contraction in the presence of AVL.

Vasomotor effects of acetylcholine, bradykinin, noradrenaline, 5-hydroxytryptamine, histamine and angiotensin II on the mouse basilar artery.

We investigated the responsiveness of the mouse basilar artery to acetylcholine (ACh), bradykinin (BK), noradrenaline (NA), 5-hydroxytryptamine (5-HT), histamine (His) and angiotensin (Ang) II in order to characterize the related receptor subtypes in vitro. ACh and BK induced endothelium-dependent relaxation of precontracted arteries with U-46619 (a thromboxane A2 analogue). Atropine (a non-selective muscarinic receptor antagonist) and Nω-nitro-L-arginine (a NO synthase inhibitor, L-NNA) shifted the concentration-response curve for ACh to the right, whereas pirenzepine, methoctramine and pFHHSiD (muscarinic M1, M2 and M3 antagonists, respectively) had no significant effect. L-NNA and HOE140 (a B2 antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg(9)-[Leu(8)]-BK (a B1 antagonist) and indomethacin (a cyclooxygenase inhibitor) had no significant effect. NA failed to produce any vasomotor action. His and Ang II induced concentration-dependent contraction. Diphenhydramine (a H1 antagonist) shifted the concentration-response curve for His to the right, whereas cimetidine (a H2 antagonist) had no significant effect. Losartan (an AT1 antagonist) shifted the concentration-response curve for Ang II to the right, whereas PD123319 (an AT2 antagonist) had no significant effect. These results suggest that the H1 and AT1 receptor subtypes might play an important role in arterial contraction, whereas muscarinic receptor subtypes apart from M1, M2 and M3, and B2 receptors on the endothelium, might modify these contractions to relaxations.

Bradykinin induces NO and PGF2α production via B2 receptor activation from cultured porcine basilar arterial endothelial cells.

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B2 receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H2, respectively, but not thromboxane A2. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH2 has different functionally active isoforms, including PGD2, PGE2, and PGF2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) and the B2 receptor antagonist HOE-140, but not the B1 receptor antagonist des-Arg(9), [Leu(8)]-BK, completely abolished it. In a functional study, PGD2, PGE2, and PGF2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF2α > PGE2 > PGD2. The cultured PBAECs produced PGD2, PGE2, and PGF2α spontaneously, and BK significantly enhanced the production of PGF2α, but not that of PGD2 and PGE2. The B2, but not B1, antagonist completely abolished the BK-enhanced production of PGF2α. These results suggest that BK induces production of NO and PGF2α simultaneously from PBAECs via B2 receptor activation.