RESUMEN
Orthosiphon aristatus has been traditionally used as a medicinal herb for various illnesses in Southeast Asia and Europe. The most dominant bioactive compound of the herb is rosmarinic acid (RosA) which has been demonstrated for its remarkable anti-inflammatory properties. This review describes the recent progress of studies on multi-target molecular pathways of RosA in relation to targeted inflammatory-associated diseases. An inclusive literature search was conducted using electronic databases such as Google Scholar, Scopus, Springer Link, PubMed, Medline, Wiley and Science Direct for studies reporting on the anti-inflammatory actions of RosA from 2008 until 2023. The keywords of the search were RosA and anti-inflammatory in relation to hepatoprotective, chondroprotective, cardioprotective, neuroprotective and toxicity. Only publications that are written in English are included in this review. The inhibition and deactivation of pro-inflammatory biomolecules by RosA were explained based on the initial inflammation stimuli and their location in the body. The activation of Nrf2/HO-1 expression to inhibit NF-κB pathway is the key mechanism for hepatoprotection. Besides NF-κB inhibition, RosA activates PPARγ to alleviate ischemia/reperfusion (I/R)-induced myocardial injury for cardioprotection. The regulation of MAPK and T-cell activation is important for chondroprotection, whereas the anti-oxidant property of RosA is the main contributor of neuroprotection. Even though less studies on the anti-inflammation of RosA extracts from O. aristatus, but the effective pharmacological properties of RosA has promoted it as a natural potent lead for further investigation.
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Orthosiphon , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Orthosiphon/metabolismo , FN-kappa B/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ácido RosmarínicoRESUMEN
Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.
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Orthosiphon , Plantas Medicinales , Animales , Antioxidantes/química , Extractos Vegetales/toxicidad , Extractos Vegetales/análisis , Orthosiphon/química , Pez Cebra , alfa-Glucosidasas , Plantas Medicinales/química , Fitoquímicos/toxicidad , AguaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Growing evidence indicates that hyperuricemia is closely associated with gut microbiota dysbiosis. Orthosiphon aristatus (Blume) Miq. (O. aristatus), as a traditional Chinese medicine, has been widely used to treat hyperuricemia in China. However, the mechanism by which O. aristatus treats hyperuricemia has not been clarified. AIM OF THE STUDY: In this study, we investigated whether the molecular mechanism underlying the anti-hyperuricemia effect of O. aristatus is related to the regulation of gut microbiota by 16S rDNA gene sequencing combined with widely targeted metabolomics. MATERIALS AND METHODS: Hyperuricemia was induced in rats by administration of 10% fructose and 20% yeast, and the uricosuric effect was assessed by measuring the uric acid (UA) levels in serum and cecal contents. Intestinal morphology was observed by hematoxylin and eosin (HE) staining. To explore the effects of O. aristatus on the gut microbiota and its metabolites, we utilized 16S rDNA gene sequencing combined with widely targeted metabolomics. Furthermore, metabolic pathway enrichment analysis was performed on the screened differential metabolites. The real time quantitative polymerase chain reaction (RT-PCR) and western blotting (WB) were used to detect the expression of relevant proteins in the key pathway. RESULTS: Our results indicated that O. aristatus intervention decreased serum UA levels and increased the UA levels in cecal contents in hyperuricemic rats. Additionally, O. aristatus improved intestinal morphology and altered the composition of the gut microbiota and its metabolites. Specifically, 16S rDNA revealed that O. aristatus treatment significantly reduced the abundance of unidentified-Ruminococcaceae and Lachnospiraceae-NK4A136-group. Meanwhile, widely targeted metabolomics showed that 17 metabolites, including lactose, 4-oxopentanoate and butyrate, were elevated, while 55 metabolites, such as flavin adenine dinucleotide and xanthine, were reduced. Metabolic pathway enrichment analysis found that O. aristatus was mainly involved in purine metabolism. Moreover, RT-PCR and WB suggested that O. aristatus could significantly up-regulate the expression of UA excretion transporter ATP-binding cassette subfamily G member 2 (ABCG2) in the intestine. CONCLUSION: O. aristatus exerts UA-lowering effect by regulating the gut microbiota and ABCG2 expression, indicating that this herb holds great promise in the treatment of hyperuricemia.
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Microbioma Gastrointestinal , Hiperuricemia , Orthosiphon , Ratas , Animales , Orthosiphon/química , Orthosiphon/metabolismo , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Intestinos , Ácido Úrico/metabolismo , MetabolómicaRESUMEN
BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.
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Orthosiphon , Extractos Vegetales , Extractos Vegetales/farmacología , Orthosiphon/química , Simulación del Acoplamiento MolecularRESUMEN
Orthosiphon stamineus Benth a traditional medicine used in the treatment of diabetes and kidney diseases. Sodium-glucose co-transporter (SGLT1 and SGLT2) inhibitors are the novel group of drugs used to treat patients with type 2 diabetes mellitus. In this study 20 phytochemical compounds from Orthosiphon stamineus Benth were obtained from 3 databases viz Dr.Duke's phytochemical, Ethno botanical database and IMPPAT. They were subjected to physiochemical, drug likeliness, and ADMET and toxicity predictions. Homology modeling and molecular docking against SGLT1 and SGLT2 were performed and the stability of the selected drug molecule was validated by molecular dynamic (MD) simulation for 200 ns. Among the 20 compounds, 14-Dexo-14-O-acetylorthosiphol Y alone showed higher binding affinity with SGLT1 and SGLT2 protein with the binding energy of -9.6 and -11.4 Kcal/mol respectively and had highest affinity towards SGLT2 inhibitor. This compound also satisfied Lipinski rule of 5 and had a good ADMET profile. The compound is non-toxic to marine organisms and to normal cell lines and non-mutagenic. The RMSD value attained equilibrium at 150 ns with the stability around 4.8 Å and no significant deviation was reported from 160 to 200 ns for SGLT2. Our study suggests that 14-Dexo-14-O-acetylorthosiphol Y showed promising results against the SGLT2 and could be considered as a potent anti-diabetic drug.Communicated by Ramaswamy H. Sarma.
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Diabetes Mellitus Tipo 2 , Orthosiphon , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Transportador 2 de Sodio-Glucosa/química , Transportador 2 de Sodio-Glucosa/metabolismo , Transportador 2 de Sodio-Glucosa/uso terapéutico , Orthosiphon/química , Orthosiphon/metabolismo , Simulación de Dinámica Molecular , Fitoquímicos/uso terapéuticoRESUMEN
Orthosiphon stamineus leaves (Java tea) extract is traditionally used for the treatment of urinary tract infections. According to recent in vitro data, animal infection studies, and transcriptomic investigations, polymethoxylated flavones from Java tea exert antiadhesive activity against uropathogenic Escherichia coli (UPEC). This antiadhesive activity has been shown to reduce bladder and kidney lesion in a mice infection model. As no data on the antivirulent activity of Java tea intake on humans are available, a biomedical study was performed on 20 healthy volunteers who self-administered Orthosiphon infusion (4 × 3 g per day, orally) for 7 days. The herbal material used for the study conformed to the specification of the European Pharmacopoeia, and ultra high-performance liquid chromatography (UHPLC) of the infusion showed rosmarinic acid, caffeic acid, and cichoric acid to be the main compounds aside from polymethoxylated flavones. Rosmarinic acid was quantified in the tea preparations with 243 ± 22 µg/mL, indicating sufficient reproducibility of the preparation of the infusion. Urine samples were obtained during the biomedical study on day 1 (control urine, prior to Java tea intake), 3, 6 and 8. Antiadhesive activity of the urine samples was quantified by flowcytometric assay using pre-treated UPEC NU14 and human T24 bladder cells. Pooled urine samples indicated significant inhibition of bacterial adhesion on day 3, 6 and 8. The urine samples had no influence on the invasion of UPEC into host cells. Bacterial proliferation was slightly reduced after 24 h incubation with the urine samples. Gene expression analysis (qPCR) revealed strong induction of fitness and motility gene fliC and downregulation of hemin uptake system chuT. These data correlate with previously reported datasets from in vitro transcriptomic analysis. Increased bacterial motility was monitored using a motility assay in soft agar with UPEC UTI89. The intake of Java tea had no effect on the concentration of Tamm-Horsfall Protein in the urine samples. The present study explains the antiadhesive and anti-infective effect of the plant extract by triggering UPEC from a sessile lifestyle into a motile bacterial form, with reduced adhesive capacity.
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Flavonas , Orthosiphon , Escherichia coli Uropatógena , Animales , Ratones , Humanos , Orthosiphon/química , Reproducibilidad de los Resultados , Antibacterianos/farmacología , Hojas de la Planta/química , Flavonas/farmacología , Modelos Animales de Enfermedad , Ácido RosmarínicoRESUMEN
<b>Background and Objective:</b> <i>Orthosiphon</i> sp., contains many active ingredients that are beneficial to health. In addition to prevention, they are also used in treatment. This study aims to evaluate the agronomic characteristics of 9 <i>Orthosiphon</i> sp., based on morphology and combine molecular biology methods to determine the genetic relationship based on the "ITS1-4" gene region. <b>Materials and Methods:</b> Nine seed samples/species <i>Orthosiphon</i> sp., grown in 9 provinces in South Vietnam were collected and planted for survey at the Can Tho experimental farm. The method of observing and describing the external morphology and microdissection of the eye cage is carried out. The DNA extraction was performed at the Molecular Biology Laboratory, Institute of Food and Biotechnology, Can Tho University. <b>Results:</b> There are differences in some parameters except leaf width and flower diameter. A simple pedigree chart can classify nine cat breeds into 3 groups: Group I includes An Giang (Râ1), Ca Mau (Râ2) and Can Tho (Râ3) breeds that are genetically close to each other and have only the same quantity, group II includes 2 varieties of Vinh Long (Râ8) and Dong Thap (Râ6), group III includes 4 identical samples in Kien Giang (Râ7), Hau Giang (Râ4), Soc Trang (Râ5) and Tien Giang (Râ9). <b>Conclusion:</b> With molecular biology techniques, 9 cat breeds have been identified, all belonging to the species <i>Orthosiphon aristatus</i>. However, to have more accurate and complete conclusions, it is necessary to study some specific gene sequences related to the morphology and substances contained in the plant.
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Orthosiphon , Plantas Medicinales , Humanos , Fitomejoramiento , Agricultura , BiotecnologíaRESUMEN
BACKGROUND: Pancreatic cancer is the most aggressive cancer type. Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients. AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model. METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively. RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents. CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.
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Orthosiphon , Neoplasias Pancreáticas , Animales , Humanos , Ratones , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Desoxicitidina/análogos & derivados , Eosina Amarillenta-(YS)/farmacología , Eosina Amarillenta-(YS)/uso terapéutico , Gemcitabina , Xenoinjertos , Antígeno Ki-67/metabolismo , Ratones Desnudos , Necrosis , Orthosiphon/metabolismo , Neoplasias Pancreáticas/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias PancreáticasRESUMEN
BACKGROUND: Orthosiphon stamineus Benth (O.S) is a traditional south-east Asian herb. The extract of O.S is used in the formulation of ethanolic nanolipid vesicle system to have considerable potential for tumour therapeutics. METHODS: The research objective is to develop and characterise the anticancer and antiangiogenic effect of O.S extract in the form of nano-ethanolic spherosomes (ESP) using phospholipids in melanoma. Spherosomes formulation of O.S was developed using the thin-film re-hydration method and converted to gel using Acrypol 1%. The formulations were subjected to optimisation and physical-chemical characterisations like particle size, surface charge, DSC, FTIR, and TEM. Cytotoxicity of O.S and ESP was studied using an endothelial cell line (EA. hy926). Furthermore, anti-melanoma effect of O.S spherosome gel was studied in albino mice after topical administration. RESULTS: ESP-6 with the ratio of extract (O.S): cholesterol: phospholipid (1: 6: 0.5) showed the highest entrapment efficiency (80.56 ± 0.84%) using ultraviolet spectroscopy. In-vivo permeation/penetration studies revealed deeper absorption of ESP-6 compared to a hydroethanolic gel of O.S. In-vitro and in vivo anti-melanoma studies demonstrated the significant tumour-suppressing effect of ESP-6 on murine melanoma. Percentage inhibition of tumour growth by O.S and ESP-6 at 3000 mg/kg showed to be 63.98 ± 7.86% and 87.76 ± 7.90%, respectively. CONCLUSION: Spherosome vesicles were developed with a smooth surface. The results demonstrated that O.S extract showed no toxicity when tested on the endothelial cell line. O.S loaded in spherosomes has the potential to lower the growth of melanoma in mice. The spherosomes loaded with O.S do not promote tumour growth or act as antiangiogenetic in melanoma.
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Neoplasias , Orthosiphon , Animales , Gotas Lipídicas , Ratones , Orthosiphon/química , Fosfolípidos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
(1) Background: Orthosiphon stamineus Benth. is a traditional medicine used in the treatment of diabetes and chronic renal failure in southern China, Malaysia, and Thailand. Diabetes is a chronic metabolic disease and the number of diabetic patients in the world is increasing. This review aimed to systematically review the effects of O. stamineus in the treatment of diabetes and its complications and the pharmacodynamic material basis. (2) Methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the databases ScienceDirect, PubMed, and Web of Science. (3) Results: Thirty-one articles related to O. stamineus and diabetes were included. The mechanisms of O. stamineus in the treatment of diabetes and its complications mainly included inhibiting α-amylase and α-glucosidase activities, antioxidant and anti-inflammatory activities, regulating lipid metabolism, promoting insulin secretion, ameliorating insulin resistance, increasing glucose uptake, promoting glycolysis, inhibiting gluconeogenesis, promoting glucagon-likepeptide-1 (GLP-1) secretion and antiglycation activity. Phenolic acids, flavonoids and triterpenoids might be the main components for hypoglycemia effects in O. stamineus. (4) Conclusion: O. stamineus could be an antidiabetic agent to treat diabetes and its complications. However, it needs further study on a pharmacodynamic substance basis and the mechanisms of effective constituents.
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Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Orthosiphon/química , Diabetes Mellitus/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacocinética , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Medicina Tradicional de Asia Oriental , Extractos Vegetales/química , Extractos Vegetales/farmacología , Plantas Medicinales/químicaRESUMEN
Orthosiphon stamineus (O.S) is widely consumed for its medidcinal value including anti-inflammatory, anti-infective, and diuretic properties. The present study evaluates the cytoprotective, anti-mutagenic, and anticlastogenic efficacies of standardized extract of Orthosiphon stamineus. Normal liver cell line (WRL68) exposed to hydrogen peroxide and serum-deprived media as insults to evaluate cytoprotective and glutathione activation activities of (Et. O. s). Salmonella typhimurium TA98 and TA100 exposed to different concentrations of (Et. O. s). The influence of Et. O. s on mitotic, replicative indices as well as chromosomal aberration (CA) and sister chromatid exchange (SCE) induced in human peripheral blood lymphocytes by mitomycin C (MMC). The Et. O.s proved to be a potent scavenger for hydrogen peroxide and other free radicals in serum-depraved media, which showed to stimulate glutathione production in liver cells line. Moreover, it did not induce mutations in S. typhimurium subspecies TA98 and TA100. The standardized extract exhibited powerful antimutagenic activities as verified against both 2-nitrofluorene and sodium azide in S. typhimurium TA98 and TA100 cells, respectively. Cytogenetic tests showed high concentrations of Et. O. s to reduce the values of mitotic and replicative indices without any accompanying side effects, such as chromosomal abnormalities or SCE. To ameliorate MMC effects, pretreatment with the extract proofed to be efficient protocol. These data suggests that O. stamineus extract could be useful as cytoprotective, antimutagenic, and anticlastogenic efficacies, which owes to its potent chemoprevention, antioxidant, and glutathione activation properties.
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Antimutagênicos , Orthosiphon , Antimutagênicos/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Etanol/toxicidad , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la PlantaRESUMEN
Urinary tract infections influence the mortality rate in pigs and are linked to extensive antibiotic usage in the farm industry. Filipendula ulmaria (L.) Maxim. and Orthosiphon aristatus (Blume) Miq. are widespread medicinal plants traditionally used to treat urinary tract disorders. As their preparations are orally administered, the metabolism of their constituents by gut microbiota before absorption should be considered. Until now, no experiments had been performed to describe the biotransformation of tthose plants' extracts by animal gut microbiota. The study evaluates the influence of pig intestinal microbiota on the structure of active compounds in flowers of F. ulmaria and leaves of O. aristatus. The incubations of the extracts with piglet gut microbiota were performed in anaerobic conditions, and the samples of the batch culture were collected for 24 h. In F. ulmaria, the main metabolites were quercetin and kaempferol, which were products of the deglycosylation of flavonoids. After 24 h incubation of O. aristatus extract with the piglet gut microbiota, 2 main metabolites were observed. One, tentatively identified as 3-(3-dihydroxyphenyl)propionic acid, is likely the primary metabolite of the most abundant depsides and phenolic acids. The results confirm the formation of the compounds with anti-inflammatory and diuretic activity in the microbiota cultures, which might suggest F. ulmaria and O. aristatus for treating urinary tract disorders in piglets. Based on the similarities of human and pig gut microbiota, the pig model can help estimate the metabolic pathways of natural products in humans.
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Filipendula , Microbioma Gastrointestinal , Orthosiphon , Sistema Urinario , Animales , Filipendula/química , Filipendula/metabolismo , Orthosiphon/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Porcinos , Sistema Urinario/metabolismoRESUMEN
<b>Background and Objective:</b> The cat whiskers plant (<i>Orthosiphon aristatus</i> Blume Miq) is a plant that has been widely used as raw material for traditional medicine. The population of white-purple varieties of <i>O. aristatus</i> is decreasing efforts to maintain the white-purple <i>O. aristatus</i> need to be done keeping in mind its potential as raw material for traditional medicine. This study aims to determine the composition of a suitable medium in growing plantlet <i>O. aristatus</i> white-purple varieties and the content of its secondary metabolites. <b>Materials and Methods:</b> The internode explants were induced on MS medium added by various combinations of zeatin and 2,4-Dichlorophenoxyacetic acid (2,4-D). Root induction was carried out on shoots formed on MS medium with Indole-3-Butyric Acid (IBA). The acclimatization process was carried out using soil media. Determination of secondary metabolite levels was carried out on <i>O. aristatus</i> (<i>in vitro</i> culture) and wild-type plants aged ten months using high-performance liquid chromatography (HPLC). <b>Results:</b> MS+BAP 2ppm+NAA3 ppm media was the optimal medium for growing shoots in leaf explants. Media MS+zeatin 3 ppm+2,4-D 2 ppm produced good shoot growth on internode explants. The best root induction occurred in MS+IBA media of 0.75 ppm. The acclimatization process was successful on shoots originating from the internode, while those from leaf explants had not succeeded in growing and developing. <b>Conclusion:</b> The levels of rosmarinic acid and sinensetin in the white-purple variety <i>O. aristatus</i> (<i>in vitro</i> culture) were 1.08 and 1.62% w/w and higher than those of wild varieties.
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Ácido 2,4-Diclorofenoxiacético/química , Agricultura/métodos , Flavonoides/química , Orthosiphon/química , Hojas de la Planta/metabolismo , Zeatina/química , Cromatografía Líquida de Alta Presión , Cinamatos , Color , Medios de Cultivo , Depsidos , Extractos Vegetales/farmacología , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/química , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/crecimiento & desarrollo , Ácido RosmarínicoRESUMEN
BACKGROUND: Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, many patients with advanced pancreatic cancer become insensitive towards gemcitabine treatment. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate the complementary effects of an ethanolic extract of O.s (Et. O.s) or rosmarinic acid in combination with gemcitabine on Panc-1 pancreatic cancer cells. METHOD: Cell viability and colony formation assays were used to determine the 50% inhibitory concentration (IC50) of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using Quantitative Real-time PCR (QPCR), flow cytometry and immunohistochemistry. RESULTS: Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing the gene expression of multidrug-resistant protein family (MDR) (MDR-1, MRP-4, and MRP-5) and molecules related to epithelial-mesenchymal transition (ZEB-1 and Snail-1). An induction of the human equilibrate nucleoside transporter-1 (hENT-1) gene was also found in cells treated with Et. O.s-gemcitabine. The Et. O.s-gemcitabine combination induced cellular senescence, cell death and cell cycle arrest in Panc-1. In addition, the inhibition of Notch signalling was demonstrated through the downregulation of Notch 1 intracellular domain in this treatment group. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, epithelial mesenchymal transition (EMT) markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain. CONCLUSION: This study provides valuable insights on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro, suggesting its potential use as a novel complementary treatment in pancreatic cancer patients.
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Orthosiphon , Neoplasias Pancreáticas , Apoptosis , Línea Celular Tumoral , Cinamatos , Desoxicitidina/análogos & derivados , Depsidos , Humanos , Orthosiphon/química , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Gemcitabina , Ácido RosmarínicoRESUMEN
Orthosiphon aristatus (Blume) Miq. of the Lamiaceae family, called as kumis kucing in Indonesia, is a valuable medicinal plant for their pharmacological properties. The present study comprised of fifteen genotypes of O. aristatus was undertaken to evaluate the genotypes based on phytochemical content and pharmacological activities of leaves ethanol extract. Chemometric analysis (correlation and principal component analysis) was also used to investigate the genetic variability based on phytochemical content and pharmacological activities of O. aristatus genotypes. Results of phytochemical characterization showed that total phenolic ranged from 1.48 to 36.08 (maximum in A15) mg GAE/g DW, total flavonoid ranged from 0.10 to 3.07 (maximum in A15) mg QE/g DW, sinensetin ranged from 0.36 to 4.02 (maximum in A11) mg/g DW, and rosmarinic acid ranged 0.06 to 7.25 (maximum in A7) mg/g DW. Antioxidant activity was tested using DPPH and FRAP assay. Antioxidant results showed that DPPH ranged from 1.68 to 15.55 (maximum in A15) µmol TE/g DW and FRAP ranged from 0.07 to 1.60 (maximum in A1 and A7) µmol TE/g DW. The genotype A8 showed the highest cytotoxic activities against HeLa (66.25%) and MCF-7 (61.79%) cell lines. Maximum α-glucosidase inhibitory activity was recorded in genotype A2 with the value of 62.84%. The genotypes A1, A2, A7, A11, and A15 were identified as superior based on their phytochemicals content and pharmacological activities coupled with chemometric analysis. This finding is important for breeding studies and also the pharmaceutical perspective of O. aristatus.
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Etanol/química , Orthosiphon/genética , Fitoquímicos/análisis , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Antineoplásicos/farmacología , Antioxidantes/farmacología , Genotipo , Inhibidores de Glicósido Hidrolasas/farmacología , Análisis Multivariante , Análisis de Componente PrincipalRESUMEN
Clerodendranthus spicatus, popularly known as "kidney tea" in China, is consumed traditionally as a functional food for treatment of renal inflammation, dysuria, and gout. We evaluated the effects of C. spicatus on gout by assessing activities of antihyperuricemia, anti-gouty arthritis, and analgesia in vivo, and the results indicated that the ethyl acetate fraction shows potential activities. Subsequent phytochemical investigation of this fraction led to the isolation of 32 compounds, consisting of 20 diterpenoids (including the new orthosiphonones E and F), 2 triterpenoids, 6 flavonoids, 2 lignanoids, and 2 phenolic acid derivatives. Pharmacological investigation of the pure compounds in the cellular model of hyperuricemia indicated that 12 compounds could promote the excretion of uric acid at 10 µg/mL, and compounds 3, 4, 5, and 21 had better effects than that of benzbromarone, a famous uricosuric drug. Furthermore, compounds 4, 6, 7, 9, 14, 15, 23, 26, and 31 showed significant anti-gouty arthritis activity in monosodium urate (MSU)-induced joint swelling at the dose of 50 mg/kg, while compounds 4, 5, 7, 9, and 26 exhibited significant inhibition of pain induced by acetic acid. Our findings provided scientific justification to support the traditional application of "kidney tea" for treating gout and suggested its good application prospects in the future.
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Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Supresores de la Gota/administración & dosificación , Supresores de la Gota/química , Gota/tratamiento farmacológico , Orthosiphon/química , Animales , China , Medicamentos Herbarios Chinos/metabolismo , Femenino , Supresores de la Gota/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Orthosiphon/metabolismo , Metabolismo Secundario , Ácido Úrico/metabolismoRESUMEN
OBJECTIVES: To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms. METHODS: Orthosiphon stamineus extracts were extracted using 50% ethanol and enriched using ethyl acetate, and characterised utilising UPLC/ESI-MS. A potassium oxonate (PO) induced hyperuricemic mouse model was used to evaluate antihyperuricemia and nephroprotective effects of O. stamineus ethyl acetate extracts (OSE). KEY FINDINGS: Eight constituents from OSE were identified and OSE treatment ameliorated HUA by regulating key indicators of kidney dysfunction and xanthine oxidase, adenosine deaminase activity and urate transporters in hyperuricemic mice. Moreover, in renal histopathology analysis, OSE significantly alleviated kidney injury. CONCLUSIONS: These findings demonstrate that OSE has antihyperuricemic and nephroprotective effects on PO-induced HUA mice and those results indicate that OSE could be a safe and effective agent or functional ingredient for treating HUA.
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Hiperuricemia/tratamiento farmacológico , Riñón/efectos de los fármacos , Orthosiphon/química , Extractos Vegetales/farmacología , Animales , Creatinina/sangre , Hiperuricemia/inducido químicamente , Riñón/metabolismo , Riñón/patología , Hígado/metabolismo , Masculino , Ratones , Transportadores de Anión Orgánico/metabolismo , Ácido Oxónico , Ácido Úrico/sangre , Xantina Oxidasa/metabolismoRESUMEN
Primarily, optimization of ultrasonic-assisted extraction (UAE) conditions of Orthospihon stamineus was evaluated and verified using a central composite design (CCD) based on three factors including extraction time (minutes), ultrasound amplitude (A), and solvent concentration (%). The response surface methodology (RSM) was performed to develop an extraction method with maximum yield and high rosmarinic acid content. The optimal UAE conditions were as follows: extraction time 21 min, ultrasound amplitudes 62 A, and solvent composition 70% ethanol in water. The crude extract was further fractionated using solid-phase extraction (SPE), where six sequential fractions that varied in polarity (0-100% Acetonitrile in water) were obtained. Next, the six fractions were evaluated for their antioxidant and anti-cancer properties. This study found that Fraction 2 (F2) contained the highest rosmarinic acid content and showed the strongest antioxidant activity. Additionally, F2 showed an anti-proliferative effect against prostate cancer (DU145) with no harmful effect on normal cells.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Orthosiphon/química , Extractos Vegetales/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Línea Celular Tumoral , Cinamatos/aislamiento & purificación , Depsidos/aislamiento & purificación , Humanos , Masculino , Modelos Químicos , Hojas de la Planta/química , Extracción en Fase Sólida , Solventes , Ultrasonido , Ácido RosmarínicoRESUMEN
Aqueous and acetone extracts of O. stamineus leaves reduce the adhesion of uropathogenic E. coli (UPEC, strain UTI89) to T24 bladder cells significantly (IC25 ~ 524â¯mg/mL, resp. 40⯵g/mL). The acteonic extract had no cytotoxic effects against UPEC in concentrations that inhibited the bacterial adhesion. The extract significantly reduced the gene expression of fimH, fimC, fimD, csgA and focG, which are strongly involved in the formation of bacterial adhesins. The antiadhesive effect was due to the presence of polymethoxylated flavones, enriched in the acetonic extract. Five flavones have been isolated by fast centrifugal partition chromatography, followed by preparative HPLC. Eupatorin, ladanein, salvigenin, sinensetin, 5,6,7,4'-tetramethoxyflavone and 5-hydroxy-6,7,3',4'-tetramethoxyflavone were identified as the main polymethoxylated flavones. With the exception of eupatorin, all of these flavones reduced the bacterial adhesion in a concentration depending manner, indicating that B-ring hydroxylation and methoxylation seems to have a major impact on the antiadhesive activity. In addition, this was confirmed by investigation of the flavones chrysoeriol and diosmetin, which had only very weak antiadhesive activity. From these data, Orthosiphon extracts can be assessed to have a pronounced antiadhesive activity against UPEC, based on a variety of polymethoxylated flavones.
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Adhesión Bacteriana/efectos de los fármacos , Flavonas/farmacología , Orthosiphon/química , Hojas de la Planta/química , Escherichia coli Uropatógena/efectos de los fármacos , Línea Celular Tumoral , Flavonas/aislamiento & purificación , Flavonoides , Alemania , Humanos , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacologíaRESUMEN
Specific recognition and bacterial adhesion to host cells by uropathogenic Escherichia coli (UPEC) are the first steps towards infection of epithelial tissue of the human urogenital system. Therefore, targeting of UPEC virulence factors, relevant for adhesion, is a promising approach for prevention of recurrent urinary tract infections (UTI). A fully characterized plant-derived aqueous extract from the leaves of Orthosiphon stamineus (OWE), a plant traditionally used in clinical practice in Europe and Asia for UTI, has been shown to exert strong antiadhesive effects under in vitro and in vivo conditions. For improved understanding of the underlying mechanisms, transcriptome analysis of OWE-treated UPEC strain UTI89 by Illumina sequencing and cross-validation of these data by qPCR indicated significant downregulation of bacterial adhesins (curli, type 1-, F1C-, and P fimbriae) and of the chaperone-mediated protein folding/unfolding and pilus assembly process; in contrast, flagellar and motility-related genes were upregulated. We conclude that OWE transforms the sessile lifestyle of bacteria into a motile one and therefore disables bacterial attachment to the host cell. Additionally, the extract inhibited gene expression of multiple iron-acquisition systems (ent, fep, feo, fhu, chu, sit, ybt). The present study explains the antiadhesive and anti-infective effect of the plant extract by pinpointing specific biochemical and molecular targets.