Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model. RESULTS: Findings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it's anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model. CONCLUSIONS: This study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.

Evaluation of the anti-inflammatory and antioxidant properties and isolation and characterization of a new bioactive compound, 3,4,9-trimethyl-7-propyldecanoic acid from Vitex negundo.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicines derived from plant extraction are affordable, more therapeutically effective, and have fewer side effects than contemporary medications. Vitex negundo L. (V. negundo). is a medicinal shrub, which contains numerous phytoconstituents. In ancient medicinal practices, V. negundo was primarily prescribed as an analgesic and anti-inflammatory drug. AIM OF THE STUDY: This study aims to evaluate the anti-inflammatory and antioxidant characteristics of crude extracts from V. negundo leaves, including those derived from petroleum ether (P), methanol (M), and aqueous (A) solvents. Additionally, the research seeks to identify the specific bioactive compounds responsible for these observed properties. MATERIALS AND METHODS: The nitric oxide scavenging study was performed to evaluate the V. negundo crude extract's ability to function as a nitric oxide scavenger. Protein denaturation and proteinase inhibition experiments were employed to study the ability of extracts to suppress proteolysis and inhibit the enzymes that cause tissue injury. The membrane-stabilizing potency of plant extracts were examined through the process of heat-induced hemolysis. The ability of the extracts to neutralize free radicals showed a dose-dependent response, and the aqueous extract exhibited substantially higher activity in both FRAP and DPPH. The GC-MS analysis of V. negundo extracts revealed a vast array of pharmacologically active metabolites. Based on this Bioassay-guided fractionation approach, the optimal extract was selected for the potent molecule isolation and characterization. RESULTS: The findings demonstrated that the aqueous extract of V. negundo exhibited markedly superior radical scavenging and anti-inflammatory capabilities compared to the other two extracts. Furthermore, a new molecule, 3,4,9-trimethyl-7-propyldecanoic acid was isolated from this extract, and its chemical structure was successfully determined. CONCLUSION: This study revealed that the aqueous extract of V. negundo demonstrated notably stronger in vitro anti-inflammatory and antioxidant properties in comparison to the methanol and petroleum ether extracts. The identified active compound, 3,4,9-trimethyl-7-propyldecanoic acid is likely responsible for the extract's free radical scavenging and anti-inflammatory effects. Furthermore, conducting both in vitro and in vivo studies is crucial to substantiate the potential of this active constituent for the development of an anti-inflammatory drug derived from V. negundo.

Vitex agnus castus effects on hyperprolactinaemia.

Background: Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods: We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results: Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion: It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

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).

Phyto-progestins for the treatment of abnormal uterine bleeding without organic cause in women at high risk for breast cancer and breast cancer survivors: a prospective, pilot study.

OBJECTIVES: Some plants, such as Dioscorea Villosa (DV), Vitex Agnus Castus (VAC) and Turnera diffusa (D) have some 'progesterone-like' properties. We have investigated their simultaneous administration in breast cancer (BC) survivors or carriers of specific genetic mutations that can increase the risk of developing BC suffering from abnormal uterine bleeding without organic cause. METHODS: Women with irregular cycles in terms of length (interval between ≤ 24 or ≥ 38 days) without a uterine organic disease (polyps, adenomyosis, fibroids, hyperplasia/malignancy) were included. A daily diary of bleeding, questionnaires about health-related quality of life (Short Form 36) and menstrual psychophysical well-being (PGWB-1) and the Greene Climacteric Scale (GCS) (in women older than 40 years old) questionnaire were used. The presence of some premenstrual syndrome (PMS) symptoms was also evaluated. RESULTS: In the analyzed group of women (n = 15), all experienced a regularization of the menstrual cycles, with a mean duration in the three months of use of 27.1 ± 3.2 days, with a significant reduction of menstrual pain (p = 0.02) and flow (p = 0.02) intensity. Women with PMS (7/15) reported an impovement in depression, headache and abdominal pain scores (p < 0.05). No specific deterioration of different questionnaires evaluated during treatment were observed. General satisfaction with the treatment was 6.8 ± 0.3/10 on a 10 point. CONCLUSIONS: A combination of DV, VAC and D could be a promising candidate to treat menstrual irregularities without an organic cause, with a significant reduction of menstrual pain and flow intensity and possible additional benefits in PMS symptoms treatment in women at genetic risk for BC and BC survivors.

New Halogenated Flavonoids from Adenosma bracteosum and Vitex negundo and Their α-Glucosidase Inhibition.

Adenosma bracteosum and Vitex negundo are natural sources of methoxylated flavonoids. Little is known about the α-glucosidase inhibition of multi-methoxylated flavonoid derivatives. Eighteen natural flavonoids were isolated from A. bracteosum and V. negundo. Seven halogenated derivatives were synthesized. Their chemical structures were elucidated by extensive NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. All compounds were evaluated for their α-glucosidase inhibition. Most compounds showed good activity with IC50 values ranging from 16.7 to 421.8 µM. 6,8-Dibromocatechin was the most active compound with an IC50 value of 16.7 µM. A molecular docking study was conducted, indicating that those compounds are potent α-glucosidase inhibitors.

El alivio natural: Sauzgatillo (Vitex agnus-castus) para el síndrome premenstrual y la dismenorrea / The natural relief: Chasteberry (Vitex agnus-castus) for premenstrual syndrome and dysmenorrhea

El síndrome premenstrual es un trastorno común en mujeres en edad reproductiva y se caracteriza por al menos un síntoma físico, emocional o conductual, que aparece en la fase lútea del ciclo menstrual y se resuelve poco después del inicio de la menstruación. Los tratamientos convencionales para el dolor perimenstrual cíclico tienen inconvenientes que incluyen efectos secundarios, interferencia con la función reproductiva de las mujeres o escasa efectividad en el alivio de los síntomas. Muchas mujeres recurren a terapias naturales para tratar una gran variedad de síntomas menstruales. Esta revisión se centra en una de esas opciones naturales, el Sauzgatillo (Vitex agnus-castus). Se realizó una búsqueda e identificación de artículos publicados hasta mayo de 2022 recopilados por medio de sistemas de búsqueda electrónicos como Google Scholar, Medline, PubMed y Scopus. Las palabras de búsqueda fueron: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre el síndrome premenstrual y la dismenorrea.

Premenstrual syndrome is a common disorder in women of reproductive age and is characterized by at least one physical, emotional, or behavioral symptom, which appears in the luteal phase of the menstrual cycle and resolves shortly after the onset of menstruation. Conventional treatments for cyclical perimenstrual pain have drawbacks that include side effects, interference with womens reproductive function, or limited effectiveness in relieving symptoms. Many women turn to natural therapies to treat a wide variety of menstrual symptoms. This review focuses on one of those natural options, Chasteberry (Vitex agnus-castus). The information available until May 2022 was collected via the library and electronic search systems such as Google Scholar, Medline, PubMed, and Scopus. The search words were: “Premenstrual syndrome”, “dysmenorrhea” AND “Vitex agnus-castus”. Preclinical studies point to a mechanism of action in its involvement in the serotoninergic system, as well as its binding to dopamine receptors. Clinical studies prove safety and positive effect on premenstrual syndrome and dysmenorrhea.

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.

Anti-bacterial Effect and Characteristics of Gold Nanoparticles (AuNps) Formed with Vitex negundo Plant Extract.

Our current study reports the anti-bacterial activity of the gold nanoparticles (AuNps) synthesized by the green synthesis method using Vitex negundo plant leaves. The aqueous extract of Vitex negundo plant leaves are acting as the capping and stabilizing agent in the synthesis of AuNps. It is already evident from earlier studies that Vitex negundo is an abundant source of polyphenols, flavonoids, terpenoids, and many other biologically active compounds. The present study reveals the potential of biologically active compounds from the plant in the reduction reaction of chloroauric acid (HAuCl4) into gold nanoparticles. The green synthesis method is adapted instead of the chemical method, which is toxic and more expensive. The gold nanoparticles subjected to characterization with the help of UV-visible spectroscopy, FTIR to determine functional groups, light scattering to estimate size and uniformity, scanning emission microscopy with EDX for accurate size and shape of AuNps, and X-ray diffraction to reveal the crystalline structure. The characteristics of AuNps formed are UV reading at 520 nm, FTIR showing the presence of phenols and alkenes, DLS, SEM, and XRD confirming the spherical shape with the size around 70-90 nm. The anti-bacterial activity of the gold nanoparticles is evaluated against four different species of bacteria, each two gram-positive and gram-negative. The gold nanoparticles formed by Vitex negundo show good anti-bacterial activity against Salmonella typhi and M. luteus bacteria with a zone of inhibition of 6 mm and 2 mm respectively. Furthermore, the cytotoxic activities of the gold nanoparticles are yet to be known to their full extent.

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.

Evaluation of anticandidal activities and phytochemical examination of extracts prepared from Vitex agnus-castus: a possible alternative in treating candidiasis infections.

BACKGROUND: Candidiasis infection is associated with high morbidity and mortality. Fungicidal resistance of some commercially used fungicides ascended the need for a naturally effective alternative. The current study aimed to evaluate the fungicidal activity of Vitex agnus-castus extracts in vitro against some Candida species. METHODS: The bioactive compounds contained in the crude and alcoholic extracts were compared, and the antioxidant activity was tested, as well. The phytochemical analysis was carried out by Fourier Transform-Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectrometry (GC/MS). The scavenger activity of the tested extracts was tested, as well. The anticandidal activity was tested to detect the effect of the tested extracts on the mycelial growth of Candida albicans, Candida krusei, Candida parapsilosis, Candia tropicalis, Candida famata, Candida rhodotorula, and Candida dublinesis. The minimum inhibitory concentrations were calculated for all reported activities. The Scanning Electron Microscopy (SEM) and the Transmission Electron Microscopy (TEM) were used to detect the morphological and ultrastructure response in some selected species. RESULTS: FTIR and GC/MS revealed the existence of different bioactive chemical groups such as polyphenols, fatty acids, terpenes, terpenoids, steroids, aldehydes, alcohols, and esters, phytol which is a diterpene. DPPH results confirmed the antioxidant activity of all extracts where the methanolic extract was the strongest scavenging substrate. All extracts showed strong inhibitory effects against different species at a concentration of 200 µg/ml (P < 0.001). SEM and TEM showed morphological and ultrastructure changes in C. famata. CONCLUSION: The current study suggested a reliable antifungal activity of different extracts of Vitex agnus-castus against different Candida species and strains. However, further studies are required to confirm the safety of these extracts to be used in medical applications.

Vitex negundo protects against cerebral ischemia-reperfusion injury in mouse via attenuating behavioral deficits and oxidative damage.

Global cerebral ischemia/reperfusion (I-R) injury often results in an irreparable brain damage like behavioral impairment and neuronal death. This neurological complication involves diverse intricate pathological mechanisms like oxidative stress, inflammation, and apoptosis. Recently, the therapeutic value of plant-based polyphenols has gained researcher's attention. The present study focused on the putative neuroprotective role of negundoside on behavioral and oxidative stress status in an experimental model of global cerebral ischemia and reperfusion-induced brain injury. Negundoside was isolated from the leaves of Vitex negundo Linn. by chromatography for investigating its possible neurobehavioral and neuropharmacological implications. Healthy Balb/C mice of either sex were subjected to 10 min of global cerebral ischemia (GCI) followed by 24-h reperfusion. Mice were pre-treated intraperitoneally with negundoside at varying doses (1, 3, 5, 10, and 15 mg/kg) 60 min before the induction of GCI. Mice were later subjected to a battery of behavioral tests for evaluating memory-related and motor abilities. Elevated plus maze (EPM) was used to determine the anxiety levels and short-term memory whereas motor abilities were evaluated by inclined beam-walking test, rotarod, and lateral push test. TBARS and reduced glutathione (GSH) content in brains were analyzed spectrophotometrically as oxidative stress markers. Behavioral study revealed enhanced anxiety-related responses and motor deficits in I-R injured mice. Additionally, GSH and TBARS levels were found to be altered following I-R-induced neuronal injury. Contrastingly, negundoside administration was able to alleviate the behavioral and biochemical alterations to the normal levels. Together, our findings provide preliminary evidence of neuroprotective role of negundoside against global cerebral ischemia and reperfusion-induced behavioral dysfunction and oxidative damage in mice brain.

Molecular docking and simulation studies of natural compounds of Vitex negundo L. against papain-like protease (PLpro) of SARS CoV-2 (coronavirus) to conquer the pandemic situation in the world.

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is ß-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the treatment of COVID-19. The inhibition of proteases essential for the proteolytic treatment of viral polyproteins is a conventional therapeutic strategy for conquering viral infections. In the study, molecular docking approach was used to screen potential drug compounds among the phytochemicals of Vitex negundo L. against COVID-19 infection. Molecular docking analysis showed that oleanolic acid forms a stable complex and other phyto-compounds ursolic acid, 3ß-acetoxyolean-12-en-27-oic acid and isovitexin of V. negundo natural compounds form a less-stable complex. When compared with the control the synergistic interaction of these compounds shows inhibitory activity against papain-like protease (PLpro) of SARS CoV-2 (COVID-19). The molecular dynamics (MD) simulation (50 ns) were performed on the complexes of PLpro and the phyto-compounds viz. oleanolic acid, ursolic acid, 3ß-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PLpro protein binding site. The MD simulation study provides more insight into the functional properties of the protein-ligand complex and suggests that these molecules can be considered as a potential drug molecule against COVID-19. In this pandemic situation, these herbal compounds provide a rich resource to produce new antivirals against COVID-19.Communicated by Ramaswamy H. Sarma.

Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5ßH-9ßH-iridoid-1α-O-(6'-O-(6,7-dihydrofoliamenthonyl)-ß-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6'-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal

Analysis of Unani coded formulation on the hormonal parameters of patients with polycystic ovarian syndrome.

The effect of Unani coded polyherbal formulations (Picolin) containing: 1) Cinnamomum verum (Bark), 2) Glycyrrhiza glabra (Root), 3) Linum usitatissimum (Seed) and 4) Vitex agnus castus (Seed) on the hormonal levels of polycystic ovarian syndrome (PCOS) patients (n=73) was determined. A randomized controlled multi-center trial was conducted on three groups that received either: 1) Capsule Picolin (n=25, 500 mg, two capsules thrice a day) and 2) Hydroalcoholic extract, tablet Picolin-E (n=23, 250 mg thrice a day) or 3) Metformin (n=25, 500 mg, twice a day) that continued for 12 weeks. The effect of capsule Picolin before and after treatment on serum insulin (14.8±1.8 vs 10.7±1.7µIU/mL) and prolactin (17.7±0.9 vs 8.5±1.1ng/mL) levels were significant. Likewise, the tablet Picolin-E also demonstrated significant effect on serum insulin (16.7±1.7 vs 9.3±0.1µIU/mL) and prolactin (18.5±1 vs 10±1.5ng/mL) levels. On the contrary in metformin treated group these parameters, serum insulin (17.4±1.6 vs 16.4±1.4µIU/mL) and prolactin (21.7±2.8 vs 21±2.8ng/mL) were non-significant. The improvement in the menstrual flow in the PCOS patients after treatment with either capsule Picolin, tablet Picolin-E or metformin were improved by 84%, 61% and 54%, respectively. Unani formulation were comparatively more effective than metformin. The treatment effectiveness was capsule Picolin> tablet Picolin-E>metformin.

A herbal treatment approach for the management of clinical, hormonal and ultrasound parameters in reproductive age group women with polycystic ovarian syndrome: A randomized clinical trial.

Around fifteen percent women of reproductive age have been effected by Polycystic Ovarian Syndrome (PCOS); a complicated disorder; and apparently there is no standard therapy available. Considering this lack, we design present work; for the assessment of a herbal medicine (Femitex-SP4) in managing PCOs. During 2016-17; this study was carried out at Abbasi Shaheed hospital, Karachi, Pakistan. A total of 150 patients aged between 18-44 years were included as per Rotterdam criteria. Patients received 500 mg of powdered herbs in capsule form twice daily. The primary outcomes were regular menstruation and ovulation plus change in fasting blood sugar levels. Changes in free testosterone levels and ovarian morphology was secondary outcome measures. Continuous outcomes before and after treatment were compared by Student's t-test (one tailed, independent). P = 0.05 was considered as significant. Women menstrual cycle was considerably improved. Fasting blood sugar levels did not change (p=0.103392). Progesterone levels were same at the starting point and after treatment (P=0.318322). With complete recovery in 6 patients; a notable change was found in ovarian size. Free testosterone levels were also dropped significantly (p<0.00001). Our main success was drastic improvement in normalizing menstrual cycle during therapy. Herbal treatment is proven to be clinically effective in most of the patients; particularly PCOs patients with menstrual irregularities. Hence, Femitex-SP4 can be taken as a better treatment for PCOs.

Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats.

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called "Man HyungJa" in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

Azaphilones from an Endophytic Penicillium sp. Prevent Neuronal Cell Death via Inhibition of MAPKs and Reduction of Bax/Bcl-2 Ratio.

Fourteen azaphilone-type polyketides (1-14), including nine new ones (1-6 and 8-10), were isolated from cultures of Vitex rotundifolia-associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3, 6, 7, and 11-14 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure-activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.

The Cyr61 Is a Potential Target for Rotundifuran, a Natural Labdane-Type Diterpene from Vitex trifolia L., to Trigger Apoptosis of Cervical Cancer Cells.

Cervical cancer is a common female malignant tumor that seriously threatens human health. This study explored the anticervical cancer effects and potential mechanisms of Rotundifuran (RTF), a natural product isolated from Vitex trifolia L. In this study, we found that RTF can suppress the proliferation of cervical cancer cell lines, including HeLa and SiHa cells (with the IC50 less than 10 µM), via induction of apoptosis in vitro, and the antitumor effect of RTF is further confirmed on the HeLa cell-inoculated xenograft model. In addition, our results proved that the antitumor effects of RTF might be related with the reactive oxygen species- (ROS-) induced mitochondrial-dependent apoptosis through MAPK and PI3K/Akt signal pathways. Using proteomics analysis and the drug affinity responsive target stability- (DARTS-) combined mass spectrometry (DARTS-MS), Cyr61 was indicated as a potential target for RTF in cervical cancer cells. Our present study would be beneficial for the development of RTF as a candidate for treatment of cervical cancer in the future.

The network pharmacology integrated with pharmacokinetics to clarify the pharmacological mechanism of absorbed components from Viticis fructus extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Viticis fructus (VF) has been widely used in alleviating the swelling and pain, owning to its pharmacologically active components including agnuside, 10-O-vanilloylaucubin, luteolin and casticin. AIM OF THE STUDY: The pharmacokinetic profiles of the absorbed components from aqueous and ethanolic extracts of VF in rat plasma were performed, and explored the molecular mechanisms of absorbed components via network pharmacology. MATERIALS AND METHODS: Ultra-performance liquid chromatography-tandem mass spectroscopy (UHPLC-MS/MS) was employed to identify the absorbed components from rat plasma. Liquid-liquid extraction with ethyl acetate was used to purify the plasma samples. Plasma pharmacokinetics parameters of the components absorbed were analyzed after oral administration of both extracts. Network pharmacology was used to predict the biological functions and potential signaling pathways of VF. The anti-cancer effects of VF extract and absorbed components have been confirmed by in vitro experiments. RESULTS: The method was very sensitive with lower limit of quantification (LLOQ) of 1.0, 2.5, 0.2 and 0.5 ng/mL for agnuside, 10-O-vanilloylaucubin, luteolin and casticin, respectively. With the exception of 10-O-vanilloylaucubin which was not detected in the ethanolic extract of VF, all other components were detected in both extracts in plasma. The pharmacokinetic parameters of the four components from rat plasma were significantly different between the two extracts. According to the results of network pharmacology, the absorption components of VF are enriched in 32 key pathways, and 15 pathways are related to cancer. Ultimately, the anti-cancer effects, as well as the signaling pathways of VF ethanolic extract and absorbed components were verified by in vitro experiments. CONCLUSION: The optimized, sensitive and validated UHPLC-MS/MS method was successfully applied for the plasma pharmacokinetics comparison analysis of the two VF extracts. The combination of network pharmacology and pharmacokinetics provides a useful method to elucidate the biological effects and molecular mechanism of the absorbed components of VF.