A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

[Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species].

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Vitex rotundifolia L. f. and Vitex trifolia L.: A review on their traditional medicine, phytochemistry, pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex rotundifolia L. f. and Vitex trifolia L. belong to the genus Vitex, and Vitex rotundifolia L. f. evolved from Vitex trifolia L. Both are essential ethnic medicinal plants with a long history, commonly used to treat headaches, fever, diarrhea, hair loss, wound recovery, and other diseases. AIM OF THE REVIEW: The research status of Vitex trifolia L. and its relative species Vitex rotundifolia L. f. were reviewed from the aspects of traditional medicinal use, phytochemistry, and pharmacological activities, to provide a reference for the further development and utilization of Vitex rotundifolia L. f. and Vitex trifolia L. MATERIALS AND METHODS: In this paper, a comprehensive search of published literature was conducted through various books and online databases to obtain relevant information on Vitex rotundifolia L. f. and Vitex trifolia L. The search terms "(Vitex rotundifolia) OR (Vitex trifolia) OR (Fructus viticis)" were entered in PubMed, Web of Science, China national knowledge infrastructure (CNKI), Wanfang Data, Baidu Scholar, respectively. In addition to setting the year threshold of "2018-2022" on Baidu Scholar, other databases searched all fields and found 889, 283, 1263, 1023, and 147 articles, respectively. Among them, review, repetition, overlapping data, and other reasons were excluded, and finally, a total of 164 articles were included in the review study. RESULTS: A total of 369 compounds have been identified, including 159 terpenoids, 51 flavonoids, 83 phenylpropanoids, and 76 other compounds. Pharmacological studies have shown that Vitex rotundifolia L. f. and Vitex trifolia L. have a variety of pharmacological activities, such as anti-tumor, analgesic, antipyretic, anti-inflammatory, antioxidant, antibacterial, and estrogen-like activity. Modern clinical use for treating cold headaches, diarrhea dysentery, irregular menstruation, and other diseases. CONCLUSIONS: As traditional medicinal plants, Vitex rotundifolia L. f. and Vitex trifolia L. have wealthy chemical constituents and extensive pharmacological activities and are widely used in clinical practice from traditional to modern times. However, the research on the pharmacological activities of Vitex rotundifolia L. f. and Vitex trifolia L. is not in-depth, and the potential active components still need to be explored.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Vitex trifolia L. modulates inflammatory mediators via down-regulation of the NF-κB signaling pathway in carrageenan-induced acute inflammation in experimental rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex trifolia L. (V. trifolia L.), commonly known as the three-leaved chaste tree, is extensively employed in traditional Chinese medicine (TCM) to treat various conditions associated with inflammation. AIM OF THE STUDY: The present study aimed to delineate the molecular mechanisms responsible for the anti-inflammatory effect of V. trifolia L. in carrageenan (CA)-induced acute inflammation in experimental rats. MATERIALS AND METHODS: CA-induced rat paw edema model was adopted to investigate the anti-inflammatory effect of methanolic extract from leaves of V. trifolia L. (VTME) in vivo. Leukocyte infiltration into the site of inflammation was determined by histopathological analysis. Further, the effect of VTME on CA-induced local and systemic levels of specific cytokines was quantified by enzyme-linked immunosorbent assay (ELISA). Moreover, its impact on the nuclear translocation of nuclear factor Kappa B (NF-κB) was analyzed by employing the western blotting technique. RESULTS: VTME at the doses of 100 mg/kg and 200 mg/kg significantly inhibited the paw edema induced by CA (p < 0.05) and effectively reduced the inflammatory leukocyte infiltration. Further, VTME markedly inhibited the CA-induced levels of Interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α in tissue, and that of cytokine-induced neutrophil chemoattractant (CINC)-2/C-X-C motif chemokine (CXCL)3 and CINC-3/CXCL2 in tissue as well as in serum. On the other hand, VTME significantly upregulated the tissue concentration of anti-inflammatory cytokine IL-10. Moreover, VTME significantly attenuated the CA-induced IκBα degradation and nuclear translocation of NF-κB p65. CONCLUSIONS: Our results demonstrate the potent anti-inflammatory effect of V. trifolia L. in vivo, providing insight into its molecular mechanism, which is mediated through down-regulation of NF-κB signal transduction.

Diterpenoids with α-glucosidase inhibitory activities from the fruits of Vitex trifolia Linn.

Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.

Comprehensive identification of Vitex trifolia fruit and its five adulterants by comparison of micromorphological, microscopic characteristics, and chemical profiles.

Prevention against the adulteration of traditional Chinese medicine in an accurate way has been long exploring. Vitex trifolia fruit (VTF), as a widely used analgesic in East Asia, has frequently been found to be adulterated with five adulterants, namely Vitex cannabifolia fruit (VCF) (Fam. Verbenaceae), Vitex negundo fruit (VNF) (Fam. Verbenaceae), Piper cubeba fruit (PCF) (Fam. Lauraceae), Euphorbia lathyris seed (ELS) (Fam. Euphorbiaceae), and Vaccinium bracteatum fruit (VBF) (Fam. Ericaceae). In this study, the methods of micromorphological identification, microscopic identification, and chemical analysis were combined to distinguish VTF from its five adulterants comprehensively. As a result, the micromorphological features in terms of fruit or seed epidermis were photographed by stereomicroscopy firstly. Secondly, the microscopic characteristics of various herb powders were captured under light microscopy. Thirdly, 33 nonvolatile components and 124 volatile components in VTF were identified by ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) and comprehensive two-dimensional gas chromatography hyphenated with mass spectrometry (GC × GC-MS), respectively. Furthermore, betulinic acid, persicogenin, and the volatile 4-(2,2,6-trimethyl-bicyclo[4.1.0]hept-1-yl)-butan-2-one were screened out to be the specific markers of VTF distinctive from the adulterants. Collectively, VTF and its five adulterants were distinguished successfully by the comparison of micromorphological, microscopic characteristics, and chemical profiles.

Effects of Vitex trifolia L. leaf extracts and phytoconstituents on cytokine production in human U937 macrophages.

BACKGROUND: Dysregulation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) form the basis of immune-mediated inflammatory diseases. Vitex trifolia L. is a medicinal plant growing in countries such as China, India, Australia and Singapore. Its dried ripe fruits are documented in Traditional Chinese Medicine to treat ailments like rhinitis and dizziness. Its leaves are used traditionally to treat inflammation-related conditions like rheumatic pain. OBJECTIVE: This study aimed to investigate the effects of V. trifolia leaf extracts prepared by different extraction methods (Soxhlet, ultrasonication, and maceration) in various solvents on cytokine production in human U937 macrophages, and identify phytoconstituents from the most active leaf extract. METHODS: Fresh leaves of V. trifolia were extracted using Soxhlet, ultrasonication, and maceration in hexane, dichloromethane, methanol, ethanol or water. Each extract was evaluated for its effects on TNF-α and IL-1ß cytokine production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. The most active extract was analyzed and further purified by different chemical and spectroscopic techniques. RESULTS: Amongst 14 different leaf extracts investigated, extracts prepared by ultrasonication in dichloromethane and maceration in ethanol were most active in inhibiting TNF-α and IL-1ß production in human U937 macrophages. Further purification led to the isolation of artemetin, casticin, vitexilactone and maslinic acid, and their effects on TNF-α and IL-1ß production were evaluated. We report for the first time that artemetin suppressed TNF-α and IL-1ß production. Gas chromatography-mass spectrometry analyses revealed the presence of eight other compounds. To the best of our knowledge, this is the first report of butylated hydroxytoluene, 2,4-di-tert-butylphenol, campesterol and maslinic acid in V. trifolia leaf extracts. CONCLUSIONS: In conclusion, leaf extracts of V. trifolia obtained using different solvents and extraction methods were successfully investigated for their effects on cytokine production in human U937 macrophages. The findings provide scientific evidence for the traditional use of V. trifolia leaves (a sustainable resource) and highlight the importance of conservation of medicinal plants as resources for drug discovery. Our results together with others suggest further investigation on V. trifolia and constituents to develop novel treatment strategies in immune-mediated inflammatory conditions is warranted.

(-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation.

In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (-)-O-methylcubebin (MC), (-)-hinokinin, and (-)-cubebin, were isolated from the ethyl acetate extract of the leaves of V. trifolia, using various chromatography. Among the three isolated compounds, MC showed the strongest effects to increase intracellular lipid accumulation in 3T3-L1 cells. From the results of the elucidation of the MC's effects on the adipogenesis of 3T3-L1 cells, the downsizing of adipocytes and the promotion of the expression of adipogenesis-related proteins, as well as adiponectin, were observed. On the other hand, since the activity of MC was inhibited by antagonists of PPARγ and improved by inhibitors of the classical mitogen-activated protein kinase (MAPK) pathway and p38MAPK pathway, MC was considered to be an agonist of PPARγ, and furthermore promoted adipogenesis via the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK phosphorylation. Although MC showed similar effects to those of rosiglitazone (RO) used as a positive control, RO promoted the migration of GLUT4 from the cytoplasm to the cell membrane, whereas MC did not show such an effect. From the abovementioned results, it was considered that MC could be a lead compound for the development of antidiabetic drugs that does not show weight gain, which is a side effect of RO.

Genetic diversity and its conservation implications of Vitex rotundifolia (Lamiaceae) populations in East Asia.

Vitex rotundifolia is an important coastal and medicinal plant, and is recorded in the List of the Important Wild Plants for Conservation in China and Japan. However, an effective conservation strategy is lacking. In the present study, the genetic diversity and population structure were analyzed using phylogeographical methods based on the trnH-psbA and trnG-trnS intergenic spacers of the chloroplast DNA (cpDNA) sequences from 157 individuals from 25 sampling sites for V. rotundifolia and V. trifolia plus the internal transcribed spacer (ITS) of the nuclear ribosomal DNA (nrDNA) sequences of 177 individuals from 27 sampling sites. The results showed that V. rotundifolia and V. trifolia had eight cpDNA and two nrDNA haplotypes, respectively, and the V. rotundifolia has a low level of genetic diversity (haplotype diversity h d,cp = 0.360, h d,nr = 0.440), a more pronounced genetic differentiation among populations (population differentiation at the species level (G ST) = 0.201, population differentiation at the allele level (N ST) = 0.462), and an insignificantly different phylogeographical structure (N ST > G ST, P > 0.05). In addition, haplotype network analyses indicated that V. rotundifolia and V. trifolia have distinct haplotypes. Divergence dating based on BEAST software analyses showed that most cpDNA clades diverged in the late Pleistocene era. Demographic analysis indicated that V. rotundifolia underwent a rapid demographic expansion. Some scientific strategies are suggested for resource conservation of V. rotundifolia based on its genetic diversity and population structure.

Larvicidal activity of essential oil from Vitex negundo and Vitex trifolia on dengue vector mosquito Aedes aegypti

Abstract INTRODUCTION: The ability of Vitex trifolia and Vitex negundo essential oils to kill Aedes aegypti and Culex quinquefasciatus larvae was evaluated. METHODS: The larvae were treated with their respective essential oils at 50-125 ppm concentration. RESULTS: LC50 and LC90 for V. trifolia against Ae. aegypti and C. quinquefasciatus, and those for V. negundo against Ae. aegypti were 57.7+0.4, 77.9+0.9 ppm and 55.17+3.14, 78.28+2.23 ppm, and 50.86+0.9, 73.12+1.3 ppm, respectively. Eucalyptol and caryophyllene were the major components in Vitex trifolia and Vitex negundo essential oil, respectively. CONCLUSIONS: This study revealed potential larvicidal properties of essential oil from V. trifolia.

Chemical constituents of Viticis Fructus / 国际药学研究杂志

Objective: To investigate the chemical constituents of the fruits of Vitex trifolia Linn. var. simplicifo- lia Cham(Viticis Fructus,VF). Methods: Various column chromatographic techniques(Silica gel,Sephadex LH-20, ODS,and MCI)and preparative high performance liquid chromatography(PHPLC)were employed to separate the chem- ical constituents of the ethanolic extracts of VF. The chemical structures of the isolated compounds were identified accord- ing to the physicochemical properties as well as the NMR and MS data. Results: The isolated fifteen compounds from the ethanol extract of VF were identified as agestricin D(1),5,3’-dihydroxy-6,7,4’-trimethoxyflavanone(2),chryso- splenol D(3),casticin(4),vitetrifolin F(5),4β,10α-aromadendranediol(6),(E)-3,3’-dimethoxy-4,4’-dihydroxystilbene(7),(8R)-evofolin B(8),ω-hydroxypropioguaiacone(9),4(- 4-hydroxyphenyl)-2-butanone(10),4-hy- droxyacetophenone(11),α-hydroxyacetovanillone(12),benzyl-β-D-glucopyranoside(13),picein(14),and 4-(4’- hydroxyphenyl)-2-butanone-4’-O-β-D-glucopyranoside(15),respectively. Conclusion: Compounds 7,8,10,and 13-15 are obtained from the genus Vitex for the first time.

[Chemical constituents from fruits of Vitex trifolia var. simplicifolia].

The present study is to investigate the chemical constituents from the dried ripe fruits of Vitex trifolia var. simplicifolia The compounds were isolated by using a variety of chromatographic methods including silicagel, ODS, Sephadex LH-20, reversed-phase HPLC, and other methods. Their structures were identified by NMR, and MS date. As a result, 18 compounds were isolated and identified as ent-2-oxo15,16,19-trihydroxypimar-8(14)-ene (1), chrysosplenol D (2), casticin (3), luteolin (4), eupatrin (5), apigenin (6), 5,4'-dihydroxy-3,6,7-trimethoxyflavone (7), luteolin-4'-O-glucoside (8), hypolaetin-7-O-ß-D-glucopyranoside (9), swertisin (10), agestricin D (11), 5,3'-dihydroxy-6,7,4'-trimethoxyflavanone (12), tomentic acid (13), 2α,3ß,23-trihydroxyolean-12-en-28-oic acid (14), 3'-acetoxy-4'-angeloyloxy-3',4'-dihydroseselin (15), dihydrodehydrodiconiferyl alcohol (16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (17) and salicifoliol (18). Among them, compounds 1, 2, 5-15, 17 and 18 were obtained from V. trifolia var. simplicifolia Cham for the first time and compounds 1, 5, 7-11, 15, 17 and 18 were isolated from thegenus Vitex for the first time.

Terpenoids from Vitex trifolia and their anti-inflammatory activities.

A new diterpenoid glucoside, (3S,5S,6S,8R,9R,10S)-3,6,9-trihydroxy-13(14)-labdean-16,15-olide 3-O-ß-D-glucopyranoside (1), and a new iridoid glucoside, (1S, 5S,6R,9R)-10-O-p-hydroxybenzoyl-5,6ß-dihydroxy iridoid 1-O-ß-D-glucopyranoside (2), along with six known compounds (3-8) were isolated from Vitex trifolia L.. Their structures were elucidated by extensive spectroscopic analysis. All these isolated compounds were evaluated for their inhibitory effects on nitric oxide production in LPS-induced RAW 264.7 macrophages. Compounds 2, 4, 5, and 7 showed moderate inhibitory activities with IC50 values of 90.05, 88.51, 87.26, and 76.06 µM, respectively.

Chemical constituents from fruits of Vitex trifolia var. simplicifolia / 中国中药杂志

The present study is to investigate the chemical constituents from the dried ripe fruits of Vitex trifolia var. simplicifolia The compounds were isolated by using a variety of chromatographic methods including silicagel, ODS, Sephadex LH-20, reversed-phase HPLC, and other methods. Their structures were identified by NMR, and MS date. As a result, 18 compounds were isolated and identified as ent-2-oxo15,16,19-trihydroxypimar-8(14)-ene (1), chrysosplenol D (2), casticin (3), luteolin (4), eupatrin (5), apigenin (6), 5,4'-dihydroxy-3,6,7-trimethoxyflavone (7), luteolin-4'--glucoside (8), hypolaetin-7---D-glucopyranoside (9), swertisin (10), agestricin D (11), 5,3'-dihydroxy-6,7,4'-trimethoxyflavanone (12), tomentic acid (13), 2α,3,23-trihydroxyolean-12-en-28-oic acid (14), 3'-acetoxy-4'-angeloyloxy-3',4'-dihydroseselin (15), dihydrodehydrodiconiferyl alcohol (16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol (17) and salicifoliol (18). Among them, compounds 1, 2, 5-15, 17 and 18 were obtained from V. trifolia var. simplicifolia Cham for the first time and compounds 1, 5, 7-11, 15, 17 and 18 were isolated from thegenus Vitex for the first time.

The Rosiglitazone-Like Effects of Vitexilactone, a Constituent from Vitex trifolia L. in 3T3-L1 Preadipocytes.

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from Myanmar, induced adipogenesis similar to rosiglitazone (ROS), which is a TZD, in 3T3-L1 preadipocytes. In the present study, we attempted to isolate from V. trifolia those compounds that showed ROS-like effects. Among the extracts of hexane, ethyl acetate, and methanol obtained from V. trifolia, the ethyl acetate extract with the strongest ROS-like effects was purified by various chromatographic methods to obtain three known compounds: vitexilactone (1), vitexicarpin (2) and oleanolic acid (3). Among the isolated compounds, the ROS-like action of 1 was the strongest. The effects of 1 on 3T3-L1 cells during adipogenesis were compared with those of ROS. Both 1 and ROS increased lipid accumulation, the expression of adiponectin and GLUT4 in the cell membrane and decreased both the size of adipocytes and the phosphorylation of IRS-1, ERK1/2 and JNK in 3T3-L1 cells. In contrast, unlike ROS, the induction of proteins involved in lipogenesis was partial. ROS-like effects of 1 in 3T3-L1 cells were suppressed by the addition of bisphenol A diglycidyl ether (BADGE), one of a peroxisome proliferator-activated receptor γ (PPARγ) antagonists, suggesting that the action of 1 on adipocytes is mediated by PPARγ. From the results of the present study, it can be concluded that 1 is a novel insulin sensitizer candidate.

Diterpenoids with diverse scaffolds from Vitex trifolia as potential topoisomerase I inhibitor.

Eleven new compounds, including six labdane (1-6), three halimane (7-9), and two clerodane (10-11) diterpenoids and 16 known analogues (12-27), were isolated from the leaves of Vitex trifolia. The structures of 1-11 were established by extensive 1D- and 2D-NMR and HRMS spectroscopic data. The absolute configurations of compounds 3, 7, and 10 were assigned using X-ray diffraction. Compounds 1-27 were evaluated for DNA topoisomerases I (Top1) inhibitory activity and cytotoxicity against HCT 116 cells. Compounds 8 and 11 exhibited equipotent Top1 inhibitory activity to the positive control, camptothecin (CPT), at 100µM. Compounds 8, 9, 16, and 27 showed moderate cytotoxicity at low micromolar concentrations.

Screening of phytochemical properties and antimicrobial activity of Malaysian medicinal plants against aquatic bacteria

Aims: Quantitative screening of phytochemical properties and antimicrobial activities were done on some plants of importance in human medicine as traditional herbs to treat fish diseases in Malaysia. Six extracts of Vitex trifolia, Aloe vera, Strobilanthes crispus, Clinacanthus nutans, Pereskia grandifolia and Peperomia pellucida were determined for phytochemical properties and their antibacterial activities against common freshwater pathogens i.e. Streptococcus agalactiae, Aeromonas hydrophila and Enterobacter cloacae. Methodology and results: Qualitative screening of phytochemical properties in herbs were determined using conversional method for flavonoids, tannins, saponin, alkaloids steroid and glycoside The results showed flavonoid was presence in all plant extracts. For the antimicrobial activity, the aqueous and methanolic extracts were tested by using disk diffusion method. Antimicrobial assay of methanolic crude extracts (25 to 100 mg/mL) showed effectiveness against the pathogenic bacteria. Comparatively, all aqueous extracts did not show any antimicrobial activity. Strong antibacterial activity was shown by the methanolic extracts of V. trifolia, A. vera and S. crispus while moderate antimicrobial activity was shown by C. nutans, P. grandifolia and P. pellucida. Conclusion, significance and impact study: The current results indicated that the studied plants might indeed be potential sources of natural antimicrobial agents to control fish diseases.

Inhibition of Melanogenesis by Abietatriene from Vitex Trifolia Leaf Oil

Vitex trifolia L. has been used traditionally to treat various illnesses, such as inflammation, headache, migraine, and gastrointestinal infections. We analyzed and evaluated the composition of V. trifolia leaf oil. Based on the results, we isolated abietatriene from V. trifolia leaf oil and investigated the effect of V. trifolia leaf oil and its active compound abietatriene on melanogenesis in B16F10 melanoma cells. They significantly decreased melanin contents and melanogenic factors, such as tyrosinase, TRP-1, TRP-2, and MITF dose-dependently in both protein and mRNA levels. Protein and mRNA expressions were determined by Western blot analysis and quantitative real time RT-PCR. Findings indicate that V. trifolia leaf oil and abietatriene reduce melanogenesis by regulating the expression of melanogenic factors. These results suggest that V. trifolia leaf oil and abietatriene could comprise a useful therapeutic agent for treating hyperpigmentation and used as effective skin-whitening agents.