Antidepressant-like Effect of Oroxylum indicum Seed Extract in Mice Model of Unpredictable Chronic Mild Stress.

Major depressive disorder (MDD) is one life-threatening disorder that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Currently, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, could have an antidepressive property. An in vitro monoamine oxidase-A (MAO-A) inhibitory assay was used to preliminarily screening for the antidepressant effect of O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks, and the daily administration of OIS extract started from week 4. The mechanisms involved in the antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in the UCMS-induced mouse model via two possible pathways: (i) it normalized the HPA axis function via the restoration of negative feedback (decreased FKBP5 and increased GR expressions) and the reduction in the glucocorticoid-related negative gene (SGK-1), and (ii) it improved neurogenesis via the escalation of BDNF and CREB expressions in the hippocampus and the frontal cortex. In addition, an HPLC analysis of the OIS extract showed the presence of baicalin, baicalein, and chrysin as major constituents. All of the results obtained from this study emphasize the potential of OIS extract containing baicalin and baicalein as an effective and novel alternative treatment for MDD.

Approach of Supercritical Carbon Dioxide for the Extraction of Kleeb Bua Daeng Formula.

Supercritical fluid extraction (SFE) is an innovative green technology for the extraction of phytochemicals from plants. Therefore, this study aimed to evaluate the application of SFE and to optimize the extraction conditions of the Thai herbal formula, Kleeb Bua Daeng (KBD). A Box-Behnken design (BBD) with response surface methodology (RMS) was used to determine the effect of the extraction time (30-90 min), temperature (30-60 °C), and pressure (200-300 bar) on response variables including the extraction yield, total phenolic content (TPC), total flavonoid content (TFC), total carotenoid content (TCC), and total anthocyanin content (TAC) of the KBD formula. The highest percentage extraction yield (3.81%) was achieved at 60 °C, 300 bar, and 60 min of the extraction time. The highest TPC (464.56 mg gallic acid equivalents/g extract), TFC (217.19 mg quercetin equivalents/g extract), and TCC (22.26 mg ß-carotene equivalents/g extract) were all achieved at 60 °C, 250 bar, and 90 min of the extraction time. On the contrary, it was not possible to quantify the total anthocyanin content as anthocyanins were not extracted by this method. The results indicated that SFE-CO2 is a suitable method of extraction for a green recovery of phytochemicals with low and moderate polarity from the KBD formula.

Effects of the Bark Resin Extract of Garcinia nigrolineata on Chronic Stress-Induced Memory Deficit in Mice Model and the In Vitro Monoamine Oxidases and ß-Amyloid Aggregation Inhibitory Activities of Its Prenylated Xanthone Constituents.

The present study describes investigation of the effects of the bark resin extract of Garcinia nigrolineata (Clusiaceae) on the cognitive function and the induction of oxidative stress in both frontal cortex and hippocampus by unpredictable chronic mild stress (UCMS). By using behavioral mouse models, i.e., the Y-maze test, the Novel Object Recognition Test (NORT), and the Morris Water Maze Test (MWMT), it was found that the negative impact of repeated mild stress-induced learning and memory deficit through brain oxidative stress in the UCMS mice was reversed by treatment with the bark resin extract G. nigrolineata. Moreover, the prenylated xanthones viz. cowagarcinone C, cowaxanthone, α-mangostin, cowaxanthone B, cowanin, fuscaxanthone A, fuscaxanthone B, xanthochymusxanthones A, 7-O-methylgarcinone E, and cowagarcinone A, isolated from the bark resin of G. nigrolineata, were assayed for their inhibitory activities against ß-amyloid (Aß) aggregation and monoamine oxidase enzymes (MAOs).

Uncommon Terpenoids from Salvia Species: Chemistry, Biosynthesis and Biological Activities.

The search for new bioactive compounds from plant sources has been and continues to be one of the most important fields of research in drug discovery. However, Natural Products research has continuously evolved, and more and more has gained a multidisciplinary character. Despite new developments of methodologies and concepts, one intriguing aspect still persists, i.e., different species belonging to the same genus can produce different secondary metabolites, whereas taxonomically different genera can produce the same compounds. The genus Salvia L. (Family Lamiaceae) comprises myriad distinct medicinal herbs used in traditional medicine worldwide that show different pharmacological activities due to the presence of a variety of interesting specialized metabolites, including mono-, sesqui-, di-, sester-, tri-, tetra-, and higher terpenoids as well as phenylpropanoids, phenolic acid derivatives, lignans, flavonoids, and alkaloids. We herein summarize the research progress on some uncommon terpenoids, isolated from members of the genus Salvia, which are well recognized for their potential pharmacological activities. This review also provides a current knowledge on the biosynthesis and occurrence of some interesting phytochemicals from Salvia species, viz. C23-terpenoids, sesterterpenoids (C25), dammarane triterpenoids (C30), and uncommon triterpenoids (C20+C10). The study was carried out by searching various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, and ProQuest. Therefore, 106 uncommon terpenoids were identified and summarized. Some of these compounds possessed a variety of pharmacological properties, such as antibacterial, antiviral, antiparasitic, cytotoxic and tubulin tyrosine ligase inhibitory activities. Due to the lack of pharmacological information for the presented compounds gathered from previous studies, biological investigation of these compounds should be reinvestigated.

Anthraquinones, Diphenyl Ethers, and Their Derivatives from the Culture of the Marine Sponge-Associated Fungus Neosartorya spinosa KUFA 1047.

Previously unreported anthraquinone, acetylpenipurdin A (4), biphenyl ether, neospinosic acid (6), dibenzodioxepinone, and spinolactone (7) were isolated, together with (R)-6-hydroxymellein (1), penipurdin A (2), acetylquestinol (3), tenellic acid C (5), and vermixocin A (8) from the culture of a marine sponge-associated fungus Neosartorya spinosa KUFA1047. The structures of the previously unreported compounds were established based on an extensive analysis of 1D and 2D NMR spectra as well as HRMS data. The absolute configurations of the stereogenic centers of 5 and 7 were established unambiguously by comparing their calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 2 and 5-8 were tested for their in vitro acetylcholinesterase and tyrosinase inhibitory activities as well as their antibacterial activity against Gram-positive and Gram-negative reference, and multidrug-resistant strains isolated from the environment. The tested compounds were also evaluated for their capacity to inhibit biofilm formation in the reference strains.

Antidementia Effects of Alternanthera philoxeroides in Ovariectomized Mice Supported by NMR-Based Metabolomic Analysis.

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.

Natural Products from Medicinal Plants with Anti-Human Coronavirus Activities.

Since the emergence of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) first reported in Wuhan, China in December 2019, COVID-19 has spread to all the continents at an unprecedented pace. This pandemic has caused not only hundreds of thousands of mortalities but also a huge economic setback throughout the world. Therefore, the scientific communities around the world have focused on finding antiviral therapeutic agents to either fight or halt the spread of SARS-CoV-2. Since certain medicinal plants and herbal formulae have proved to be effective in treatment of similar viral infections such as those caused by SARS and Ebola, scientists have paid more attention to natural products for effective treatment of this devastating pandemic. This review summarizes studies and ethnobotanical information on plants and their constituents used for treatment of infections caused by viruses related to the coronavirus family. Herein, we provide a critical analysis of previous reports and how to exploit published data for the discovery of novel therapeutic leads to fight against COVID-19.

Marine-Derived Compounds with Potential Use as Cosmeceuticals and Nutricosmetics.

The cosmetic industry is among the fastest growing industries in the last decade. As the beauty concepts have been revolutionized, many terms have been coined to accompany the innovation of this industry, since the beauty products are not just confined to those that are applied to protect and enhance the appearance of the human body. Consequently, the terms such as cosmeceuticals and nutricosmetics have emerged to give a notion of the health benefits of the products that create the beauty from inside to outside. In the past years, natural products-based cosmeceuticals have gained a huge amount of attention not only from researchers but also from the public due to the general belief that they are harmless. Notably, in recent years, the demand for cosmeceuticals from the marine resources has been exponentially on the rise due to their unique chemical and biological properties that are not found in terrestrial resources. Therefore, the present review addresses the importance of marine-derived compounds, stressing new chemical entities with cosmeceutical potential from the marine natural resources and their mechanisms of action by which these compounds exert on the body functions as well as their related health benefits. Marine environments are the most important reservoir of biodiversity that provide biologically active substances whose potential is still to be discovered for application as pharmaceuticals, nutraceuticals, and cosmeceuticals. Marine organisms are not only an important renewable source of valuable bulk compounds used in cosmetic industry such as agar and carrageenan, which are used as gelling and thickening agents to increase the viscosity of cosmetic formulations, but also of small molecules such as ectoine (to promote skin hydration), trichodin A (to prevent product alteration caused by microbial contamination), and mytiloxanthin (as a coloring agent). Marine-derived molecules can also function as active ingredients, being the main compounds that determine the function of cosmeceuticals such as anti-tyrosinase (kojic acid), antiacne (sargafuran), whitening (chrysophanol), UV protection (scytonemin, mycosporine-like amino acids (MAAs)), antioxidants, and anti-wrinkle (astaxanthin and PUFAs).

Plasmodium stage-selective antimalarials from Lophira lanceolata stem bark.

Targeting the transmissible stages of the Plasmodium parasite that develop in the human and mosquito host is a crucial strategy for malaria control and elimination. Medicinal plants offer a prolific source for the discovery of new antimalarial compounds. The recent identification of the gametocytocidal activity of lophirone E, obtained from the African plant Lophira lanceolata (Ochnaceae), inspired the evaluation of the plant also against early sporogonic stages of the parasite development. The bioassay-guided phytochemical study led to the isolation of two known lanceolins and of a new glycosylated bichalcone, named glucolophirone C. Its stereostructure, including absolute configuration of the bichalcone moiety, was elucidated by means of NMR, HRMS, ECD and computational calculations. Lanceolin B proved to be a potent inhibitor of the development of Plasmodium early sporogonic stages indicating that the plant produces two different stage-specific antimalarial agents acting on transmissible stages in the human and mosquito host.

The ethnopharmacological literature: An analysis of the scientific landscape.

ETHNOPHARMACOLOGICAL RELEVANCE: The research into bioactive natural products originating from medicinal plants, fungi and other organisms has a long history, accumulating abundant and diverse publications. However no quantitative literature analysis has been conducted so far. AIM OF THE STUDY: Here we analyze the bibliometric data of ethnopharmacology literature and relate the semantic content to the publication and citation data so that the major research themes, contributors, and journals of different time periods could be identified and evaluated. MATERIALS AND METHODS: Web of Science (WoS) was searched to identify relevant publications. The Analyze function of WoS and bibliometric software (VOSviewer) were utilized to perform the analyses. RESULTS: Until the end of November 2018, 59,576 publications -linked to 'ethnopharmacology' indexed by WoS, published since 1958 in more than 5600 journals, and contributed by over 20,600 institutions located in more than 200 countries/regions, were identified. The papers were published under four dominating WoS categories, namely pharmacology/pharmacy (34.4%), plant sciences (28.6%), medicinal chemistry (25.3%), and integrative complementary medicine (20.6%). India (14.6%) and China (13.2%) were dominating the publication space. The United States and Brazil also had more than 8.0% contribution each. The rest of the top ten countries/regions were mainly from Asia. There were around ten-fold more original articles (84.6%) than reviews (8.4%). CONCLUSIONS: Ethnopharmacological research has a consistent focus on food and plant sciences, (bio)chemistry, complementary medicine and pharmacology, with a more limited scientific acceptance in the socio-cultural sciences. Dynamic global contributions have been shifting from developed countries to economically and scientifically emerging countries in Asia, South America and the Middle East. Research on recording medicinal plant species used by traditional medicine continues, but the evaluation of specific properties or treatment effects of extracts and compounds has increased enormously. Moreover increasing attention is paid to some widely distributed natural products, such as curcumin, quercetin, and rutin.

Kleeb Bua Daeng, a Thai Traditional Herbal Formula, Ameliorated Unpredictable Chronic Mild Stress-Induced Cognitive Impairment in ICR Mice.

Thai traditional herbal formula ''Kleeb Bua Daeng (KBD)''consists of a 1:1:1 ratio (dry weight) of three medicinal plants: Piper nigrum fruit, the aerial part of Centella asiatica and the petals of Nelumbo nucifera. Oral administration of KBD to unpredictable chronic mild stress (UCMS) mice significantly improved their cognitive function caused by chronic mild stress. Daily administration of KBD significantly decreased the serum corticosterone (CORT) and malondialdehyde (MDA) levels but increased the catalase and superoxide dismutase activities in both frontal cortex and hippocampus. The effects of KBD were similar to those caused by oral administration of vitamin E. HPLC analysis of the KBD extract revealed the presence of piperine, madecassoside, asiaticoside, luteolin-7-O-glucoside, rutin, kaempferol-3-glucoside, quercetin, kaempferol and ferulic acid as major constituents.

Effects of the Ethanol Extract of Dipterocarpus alatus Leaf on the Unpredictable Chronic Mild Stress-Induced Depression in ICR Mice and Its Possible Mechanism of Action.

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.

Chemical Constituents and Antidepressant-Like Effects in Ovariectomized Mice of the Ethanol Extract of Alternanthera philoxeroides.

The previously unreported flavone glycoside, demethyltorosaflavone B (2) and the E-propenoic acid substituted flavone, torosaflavone E (3a), were isolated together with nine previously reported metabolites, including indole-3-carbaldehyde, oleanonic acid, vanillic acid, p-hydroxybenzoic acid, altheranthin (1a), alternanthin B (1b), demethyltorosaflavone D (3b), luteolin 8-C-E-propenoic acid (4) and chrysoeriol 7-O-rhamnoside (5), from the ethanol extract of the aerial part of Althernanthera philoxeroides. The crude ethanol extract was evaluated for its in vitro estrogenic activity in MCF-7 breast cancer cell line. The crude ethanol extract was also investigated in vivo for its antidepressant-like effects on ovariectomized mice using tail suspension and forced swimming tests, while its effect on the locomotor activity was evaluated by a Y-maze test. The effect of the crude extract on the serum corticosterone level, size and volume of uterus of the ovariectomized mice were also investigated. The expression of the mouse cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF) and ß-actin mRNAs in hippocampus and frontal cortex was also evaluated, using semiquantitative reverse transcription-polymerase chain reaction. The crude extract and the isolated compounds 1a, 1b, 3a, 3b and 5, were evaluated for their inhibitory effects on monoamine oxidases (MAOs)-A and -B.

Phytochemical and pharmacological properties of essential oils from Cedrus species.

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and ß-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

Anticancer and cancer preventive compounds from edible marine organisms.

A direct impact of food on health, which demonstrates that dietary habit is one of the most important determinants of chronic diseases such as cancers, has led to an increased interest of the consumers toward natural bioactive compounds as functional ingredients or nutraceuticals. Epidemiological studies revealed that the populations of many Asian countries with high consumption of fish and seafood have low prevalence of particular type of cancers such as lung, breast, colorectal and prostate cancers. This observation has led to extensive investigations of the benefits of compounds present in edible marine organisms such as fish, marine invertebrates (mollusks, echinoderms) and marine algae as cancer chemopreventive agents. Interestingly, many of these marine organisms not only constitute as seafood delicacy but also as ingredients used in folk medicine of some East and Southeast Asian countries. The results of the investigations on extracts and compounds from fish (cods, anchovy, eel and also fish protein hydrolysates), mollusks (mussel, oyster, clams and abalone), as well as from sea cucumbers on the in vivo/in vitro anticancer/antitumor activities can, in part, support the health benefits of these edible marine organisms.

Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infections.

Ten indole alkaloids were obtained from the marine sponge-associated fungus Neosartorya siamensis KUFA 0017. We studied the antimicrobial properties of these and of three other compounds previously isolated from the soil fungus N. siamensis KUFC 6349. Only neofiscalin A showed antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE); with a minimum inhibitory concentration (MIC) of 8 µg mL(-1) against both strains. Another compound, fiscalin C, presented synergistic activity against MRSA when combined with oxacillin, although alone showed no antibacterial effect. Moreover, neofiscalin A, when present at sub-MICs, hampered the ability of both MRSA and VRE strains to form a biofilm. Additionally, the biofilm inhibitory concentration values of neofiscalin A against the MRSA and VRE isolates were 96 and 80 µg mL(-1), respectively. At a concentration of 200 µg mL(-1), neofiscalin A was able to reduce the metabolic activity of the biofilms by ∼50%. One important fact is that our results also showed that neofiscalin A had no cytotoxicity against a human brain capillary endothelial cell line.

Secondary Metabolites from the Culture of the Marine Sponge-Associated Fungi Talaromyces tratensis and Sporidesmium circinophorum.

Wortmin (1), meso-1,4-bis(4-methoxybenzyl)-2,3-butanediol (2), and a new isocoumarin derivative tratenopyrone (3) were isolated from the marine sponge-associated fungus Talaromyces tratensis KUFA 0091. A new diphenyl ether derivative, circinophoric acid (4), was isolated, together with the previously reported anthraquinones catenarin and physcion, the benzophenone monomethylsoluchrin, and ß-ergosterol-5,8-endoperoxide, from the marine sponge-associated fungus Sporidesmium circinophorum KUFA 0043. The structures of the new compounds were established based on an extensive analysis of 1D and 2D NMR spectra, and, in the case of compounds 2-4, also by X-ray analysis. All of the isolated compounds were tested for their antibacterial activity against Gram-positive and Gram-negative bacteria, and multidrug-resistant isolates from the environment, as well as for their anti-quorum sensing based on the pigment production of Chromobacterium violaceum ATCC 31523. None of the compounds exhibited either antibacterial (MIC > 256 µg/mL) or anti-quorum sensing activities. The compounds were also inactive in the antifungal (MIC > 512 µg/mL) and cancer cell line (GI50 > 150 µM) assays.

Traditional Uighur Medicine Karapxa decoction, inhibits liver xanthine oxidase and reduces serum uric acid concentrations in hyperuricemic mice and scavenges free radicals in vitro.

BACKGROUND: Karapxa decoction (KD) is a Traditional Uighur Medicine used for hepatitis, cholecystitis, gastralgia, oedema, gout and arthralgia. Because of its purported effect in gout, its effects were tested in hyperuricemic mice models induced by yeast extract paste or potassium oxonate, as well as its capacity to scavenge free radicals in vitro. METHODS: Hyperuricemia was induced in mice by yeast extract paste or potassium oxonate. KD was given orally for 14 days at 200, 400 and 800 mg/kg/day, with Allopurinol 10 mg/kg/day as positive control. Serum uric acid (UA), and liver xanthine oxidase activity (XO) were measured. Scavenging activity of KD on 1, 1-diphenyl-2-picrylhydrazyl radicals (DPP•), nitric oxide (•NO), superoxide (O2•-), efficiency against lipid peroxidation, and XO inhibition were determined in vitro. RESULTS: KD inhibited liver XO activity and reduced serum uric acid in hyperuricemic mice. KD also showed noticeable antioxidant activity, scavenging free radicals (DPP•, •NO and O2•-). It was effective against lipid peroxidation and inhibited XO in vitro. CONCLUSIONS: This study supports the traditional use of Karapxa decoction to treat hyperuricemia and gout.

Spiculisporic acid E, a new spiculisporic acid derivative and ergosterol derivatives from the marine-sponge associated fungus Talaromyces trachyspermus (KUFA 0021).

A new spiculisporic acid derivative, spiculisporic acid E (2), and a new natural product 3-acetyl ergosterol 5, 8-endoperoxide (1), were isolated, together with ergosta-4, 6, 8 (14), 22-tetraen-3-one, glaucanic acid and glauconic acid, from the culture of the marine-sponge associated fungus Talaromyces trachyspermus (KUFA 0021). All the compounds were inactive against Gram-positive and Gram-negative bacteria, and Candida albicans, as well as multidrug-resistant isolates from the environment. Spiculisporic acid E (2), glaucanic acid and glauconic acid did not show in vitro growth inhibitory activity against the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method.

Aqueous extract of dioscorea opposita thunb. normalizes the hypertension in 2K1C hypertensive rats.

BACKGROUND: Dioscorea opposita Thunb. (Huai Shan Yao, DOT), a common staple food in China, has been used for more than 2000 years in traditional Chinese medicine (TCM) to treat different systemic diseases including hypertension. The objective of this study was to investigate the possible antihypertensive effects of the aqueous extract of (DOT) in renovascular hypertensive rats as well as the mechanism in reducing blood pressure. METHODS: The two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in Wistar rats. Rats with captopril, low-dose DOT and high-dose DOT treated 2K1C groups for 6 weeks. The blood pressure, cardiac mass index (heart weight/body weight), plasma level of angiotensin-II (Ang-II), endothelin-1(ET-1), superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated. RESULTS: DOT significantly reduced mean systolic and diastolic blood pressure after treatment. DOT also significantly increased plasma SOD activity but decreased plasma MDA concentration. Renal function was improved with captopril and DOT. DOT reduced plasma Ang-II activity and plasma ET concentration. They couldalso significantly reduce the left ventricular hypertrophy and cardiac mass index. CONCLUSIONS: Our results suggest that DOT may have an antihypertensive effect on hypertension by inhibit ET-converting enzyme and antioxidant activity, which warrant further exploration.