ArticleLiterature Review

The genus Stephania (Menispermaceae): Chemical and pharmacological perspectives

Authors:
  • Uttarakhand Ayurved University, Dehradun
  • Pt. L.M.S. Govt. PG College Rishikesh
  • Department of Technical Education Government of Uttarakhand India
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The plants of the genus Stephania (Menispermaceae) are widely distributed, and have long been used in folk medicine for the treatment of various ailments such as asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Over 150 alkaloids together with flavonoids, lignans, steroids, terpenoids and coumarins have been identified in the genus, and many of these have been evaluated for biological activity. This review presents comprehensive information on the chemistry and pharmacology of the genus together with the traditional uses of many of its plants. In addition, this review discusses the structure-activity relationship of different compounds as well as recent developments and the scope for future research in this aspect.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... In Ayurveda and Sidha, the plant is being used in the treatment of various ailments, including bowel disorders, stomachache, dyspepsia, dysentery, diarrhoea, birth control, piles, urinary troubles, and heart troubles, and used as hypotensive and spasmolytic [11]. Biological investigations using in vitro and in vivo models have shown that the plant possesses multiple pharmacological effects, such as antioxidant, anti-inflammatory, cytotoxic/anticancer, analgesic, and hypoglycemic effects [12,13]. Phytochemical analyses identified the hasubanan alkaloids as the major constituents along with phenolics and flavonoids, tannins, and steroids as minor constituents [13][14][15]. ...
... Biological investigations using in vitro and in vivo models have shown that the plant possesses multiple pharmacological effects, such as antioxidant, anti-inflammatory, cytotoxic/anticancer, analgesic, and hypoglycemic effects [12,13]. Phytochemical analyses identified the hasubanan alkaloids as the major constituents along with phenolics and flavonoids, tannins, and steroids as minor constituents [13][14][15]. ...
... Quantitative analysis of polyphenolics and alkaloid content revealed that the CHF contained the highest content of phenolics (313.06 mg GAE/g dried extract), flavonoids (167.25 mg CE/ g dried extract), and alkaloids (216.97 mg AE/g dried extract), followed by EAF, AQF, and PEF (Table 1). ese results were in good agreement with the previous reports that showed the occurrence of phenolic hasubanan alkaloids as the major compounds in the CHF [13,14]. e presence of a large amount of polyphenolics and alkaloids in the CHF and its high antioxidant and cholinesterase inhibitory properties suggest that they might be attributable to the bioactivity of the extracts. ...
Article
Full-text available
Alzheimer's disease (AD) is a progressive neurological disorder characterized by loss of memory and cognition. Stephania japonica is being used as traditional medicine in the treatment of different neurological problems. In this study, we evaluated the anticholinesterase and antioxidant activities of the crude methanol extract of S. japonica and its fractions in vitro and the neuroprotective effect of the most active fraction in the scopolamine-induced mouse model of memory impairment. Among the crude extract and its fractions, chloroform fraction exerted strong inhibition of acetylcholinesterase and butyrylcholinesterase enzymes with IC 50 values of 40.06 and 18.78 µg/mL, respectively. Similarly, the chloroform fraction exhibited potent antioxidant activity and effectively inhibited the peroxidation of brain lipid in vitro. e phytochemical profile revealed the high content of polyphenolics and alkaloids in the chloroform fraction. Pearson's correlation studies showed a significant association of anticholinesterase and antioxidant activity with alkaloid and phenolic contents. Kinetic analysis showed that the chloroform fraction exhibited a noncompetitive type of inhibition. In experimental mice, the chloroform fraction restored the impaired learning and memory induced by scopolamine as evidenced by a significant decrease in latency time and increase of quadrant time in probe trial in Morris water maze task. e chloroform fraction also significantly reduced the activity of acetylcholinesterase and oxidative stress in mice. Our results suggest that the chloroform fraction of S. japonica may represent a potential candidate for the prevention and treatment of AD.
... Based on herbarium specimens, it is distributed in Doti, Panchthar, and Sindhuli districts and the river-sides of Marsyangdi, Bagmati and Koshi (Figs. 1, 2, 3, and 4). Phytochemistry Semwal et al. (2010) stated that this genus contains alkaloids, Gindarudine, tetrahydropalmitine, flavonoids lignans, steroids, terpenoids, and coumarins. Nine alkaloids are isolated from the leaves, stems, and roots; they are epihernandolinol, hasubanonine, aknadinine (Brossi 1988), N-methylcorydalmine, cyclanoline, magnoflorine, isotetrandrine, isochondodendrine, and cycleanine (Singh et al. 1981;Singh et al. 2004). ...
... S. elegans is frequently used in traditional medicine because it contains alkaloids compound on its leaves, stems, and roots. It has traditionally been used for the treatment of asthma, tuberculosis, dysentery, hyperglycaemia, cancer, malaria, fever, intestinal complaints, sleep disturbances, and inflammation in Asian and African countries (Chopra et al. 1958;Gaur 1999;Kirtikar and Basu 2004;Semwal et al. 2010). The leaf of the plant is used to cure boils, blood and dysentery as ethnomedicine of Bantar, one of the dominant ethnic groups of Morang district, Nepal (Acharya and Pokhrel 2006). ...
... Extracts of S. tetrandra and its principal active components, tetrandrine (9) and fangchinoline (10), have been used to treat autoimmune diseases, such as rheumatoid arthritis, transplant rejection and systemic lupus erythematosus (Semwal et al. 2010;Lai 2002;Sekiya et al. 2004;Seow et al. 1988). Rheumatoid arthritis patients were administered 10 g extract of S. tetrandra orally for 12 weeks in a clinical trial. ...
... The limitations of this study were the lack of description of doses and a positive control. Tetrandrine at 0.1-100 lM inhibited neutrophilmonocyte chemotactic factor-1 upregulation and adhesion to fibrinogen induced by N-formyl-methionyl-leucylphenylalanine and phorbol 12-myristate 13-acetate, and reduced production of oxygen free radical, down-regulated synthesis and release of some proinflammatory cytokines (Semwal et al. 2010). In an in vitro study, tetrandrine at 16.0 lM had potent immunosuppressive activity by suppressing the antibody synthesis by B cells, and the mitogeninduced lymphoproliferative response (Seow et al. 1988). ...
Article
Full-text available
Stephania tetrandra S. Moore (S. tetrandra) is distributed widely in tropical and subtropical regions of Asia and Africa. The root of this plant is known in Chinese as "Fen Fang Ji". It is commonly used in traditional Chinese medicine to treat arthralgia caused by rheumatism, wet beriberi, dysuria, eczema and inflamed sores. Although promising reports have been published on the various chemical constituents and activities of S. tetrandra, no review comprehensively summarizes its traditional uses, phytochemistry, pharmacology and toxicology. Therefore, the review aims to provide a critical and comprehensive evaluation of the traditional use, phytochemistry, pharmacological properties, pharmacokinetics and toxicology of S. tetrandra in China, and meaningful guidelines for future investigations. Graphic abstract:
... Based on herbarium specimens, it is distributed in Doti, Panchthar, and Sindhuli districts and the river-sides of Marsyangdi, Bagmati and Koshi (Figs. 1, 2, 3, and 4). Phytochemistry Semwal et al. (2010) stated that this genus contains alkaloids, Gindarudine, tetrahydropalmitine, flavonoids lignans, steroids, terpenoids, and coumarins. Nine alkaloids are isolated from the leaves, stems, and roots; they are epihernandolinol, hasubanonine, aknadinine (Brossi 1988), N-methylcorydalmine, cyclanoline, magnoflorine, isotetrandrine, isochondodendrine, and cycleanine (Singh et al. 1981;Singh et al. 2004). ...
... S. elegans is frequently used in traditional medicine because it contains alkaloids compound on its leaves, stems, and roots. It has traditionally been used for the treatment of asthma, tuberculosis, dysentery, hyperglycaemia, cancer, malaria, fever, intestinal complaints, sleep disturbances, and inflammation in Asian and African countries (Chopra et al. 1958;Gaur 1999;Kirtikar and Basu 2004;Semwal et al. 2010). The leaf of the plant is used to cure boils, blood and dysentery as ethnomedicine of Bantar, one of the dominant ethnic groups of Morang district, Nepal (Acharya and Pokhrel 2006). ...
Chapter
Stephania elegans:Nepali: Taro lahara, Baatule paati, Baatulapaate; Tamang Paathaa, Tam Barki, Laharache; Hindi: Nagbel, Rajpatha, Dudhiya, Sankhjadi, Satwa, Myanaru; English Elegant Tape Vine (Jain and Jain 2018).
... Recent research has shown that S. cepharantha has many pharmacological effects, such as anti-neuroinflammatory [1], anti-inflammatory [2], antiviral [3] and antitumor [4] effects. It is rich in more than 40 types of alkaloids [5], especially the main component cepharanthine, which has been reported to inhibit the growth of tumor cells by regulating autophagy [6], amino acid metabolism [7] and inhibiting NF-κB [8]. Recently, it has attracted considerable attention because of its inhibitory effect on SARS-CoV-2 [9][10][11][12][13]. ...
... The genus Stephania mainly contains three subgenera: Tetrandra, Stephania and Tortoise, which are rich in alkaloids and have attracted attention due to their extensive biological activity and broad benefits for health [5]. More and more research has shown that chloroplasts play a critical function in mediating photosynthesis; they also play an important role in genetic research, evolutionary analysis, molecular identification, improvement of plant traits and resistance to biological stress. ...
Article
Full-text available
Stephania cepharantha Hayata (S. cepharantha) is a common folk medicine herb in China with many therapeutic activities. This study used Illumina sequencing technology to construct a circular chloroplast genome map and compared it with that of other Stephania species. The genome of S. cepharantha is 158,052 bp in length, including a large single-copy region of 88,770 bp, a small single-copy region of 19,760 bp, and two reverse repeat regions of 49,522 bp. The genome encodes eight ribosomal ribonucleic acid (RNA) genes, 37 transfer RNA genes, and 85 protein-coding genes. Nucleotide variation analysis revealed that six highly variable regions of Stephania can be used as potential molecular markers for taxonomic research and evolutionary analysis. This study is the first chloroplast genome report on S. cepharantha, and it provides rich and valuable genetic information for understanding the evolutionary relationships and population inheritance of the species.
... Its root tuber has been used as a traditional folk medicine for anti-inflammatory, relieving pain, and sedation to treat cancer, fever, cough, malaria, diarrhea, bellyache, stomachache, and injuries from falls and fractures by local people [3][4][5]. A total of 40 alkaloids have been identified from the plant since the study of their chemical constituents was first reported in 1975 [6], which are divided into seven categories, including protoberberine-, aporphine-, morphine-, hasubanan-, benzylisoquinoline-, bisbenzylisoquinoline-, and azafluoranthene-type alkaloids, which have been evaluated for biological activity, such as acetylcholinesterase (AChE) inhibitory, cytotoxic, anti-inflammatory, antitumor activities [7][8][9][10]. However, these confirmed biological activities do not well explain traditional folk medicine applications of S. epigaea. ...
... Previously mentioned that the medicinal plant Stephania epigaea Lo traditionally was used to treat fever, cough, malaria, diarrhea, bellyache, injuries from falls, and fracture [3,4] and newly discovered activities of antiproliferative/ anticancer, immunomodulating, and apoptosis [7,38]. Our metabolomic analysis shows that 518 metabolites were detected from the root, stem, and flowers of S. epigaea through widely targeted metabolomics analysis. ...
Article
Full-text available
Stephania epigaea, an important traditional folk medicinal plant, elucidating its bioactive compound profiles and their molecular mechanisms of action on human health, would better understand its traditional therapies and guide their use in preclinical and clinical. This study aims to detect the critical therapeutic compounds, predict their targets, and explore potential therapeutic molecular mechanisms. This work first determined metabolites from roots, stems, and flowering twigs of S. epigaea by a widely targeted metabolomic analysis assay. Then, the drug likeness of the compounds and their pharmacokinetic profiles were screened by the ADMETlab server. The target proteins of active compounds were further analyzed by PPI combing with GO and KEGG cluster enrichment analysis. Finally, the interaction networks between essential compounds, targets, and disease-associated pathways were constructed, and the essential compounds binding to their possible target proteins were verified by molecular docking. Five key target proteins (EGFR, HSP90AA1, SRC, TNF, and CASP3) and twelve correlated metabolites, including aknadinine, cephakicine, homostephanoline, and N-methylliriodendronine associated with medical applications of S. epigaea, were identified, and the compounds and protein interactions were verified. The key active ingredients are mainly accumulated in the root, which indicates that the root is the main medicinal tissue. This study demonstrated that S. epigaea might exert the desired disease efficacy mainly through twelve components interacting via five essential target proteins. EGFR is the most critical one, which deserves further verification by biological studies.
... Its IR data indicated the presence of hydroxy groups (3314 cm À1 ) and aromatic rings (1611 and 1512 cm À1 ). The 1 H and 13 C NMR data of 4 (Tables 1 and 2) were similar to those of discretamine (13), which has also been isolated from S. pierrei in the present work. The signicant differences were the presence of an anomeric proton signal at d (C-4 0 ), and 63.0 (C-6 0 ) in the I3 C NMR spectrum. ...
... Furthermore, the location of the methoxy group at C-2 was supported by the HMBC correlation between the CH 3 O-2 signal and C-2 (d C 150.0) (see Fig. 2) and this was further conrmed by the NOESY correlation between the CH 3 O-2 and H-1 (d H 6.92) (see Fig. 3). As the substituent on tetrahydroprotoberberine molecule, including a glucose moiety, does not exert a considerable effect on the optical rotation and ECD spectrum, 49,52 the same sign of optical rotation and similar ECD curve of compound 4 ( Fig. S234 †) when compared with those of compounds 1-3 has led to a conclusion that the absolute conguration at C-13a of 4 is S. On the basis of these ndings, compound 4 is the glucoside analogue of discretamine (13). 22 Compound 4 was therefore identied as discretamine 3-O-b-D-glucopyranoside (see Fig. 1). ...
Article
Full-text available
Eight new alkaloids, which are four new tetrahydroprotoberberine alkaloids, stephapierrines A-D (1-4), and four new aporphine alkaloids, stephapierrines E-H (5-8), together with three new naturally occurring alkaloids (9-11) and thirty-four known alkaloids (12-45) were isolated from the tubers of Stephania pierrei Diels. The structures of the new compounds were elucidated by spectroscopic analysis and physical properties. The structures of the known compounds were characterized by comparison of their spectroscopic data with those previously reported. Compound 42 exhibited the strongest acetylcholinesterase (AChE) inhibitory activity, which was more active than galanthamine, the reference drug. Compound 23 showed the highest butyrylcholinesterase (BuChE) inhibitory activity, which was also more active than galanthamine. Molecular docking studies are in good agreement with the experimental results.
... One such alkaloid is glabradine, isolated from the tubers of Stephania glabra (Roxb.) Miers, which suppressed S. aureus and S. mutans with the MIC value of 50 µg/mL as well as M. gypseum, M. canis, and T. rubrum with the MIC values of 25, 25, and 50 µg/mL, respectively [154]. ...
Article
Full-text available
The emergence of multidrug-resistant bacteria and fungi requires the development of antibiotics and antifungal agents. This review identified natural products isolated from Asian angiosperms with antibacterial and/or antifungal activities and analyzed their distribution, molecular weights, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1979 to 2022. One hundred and forty-one antibacterial and/or antifungal alkaloids were identified during this period, mainly from basal angiosperms. The most active alkaloids are mainly planar, amphiphilic, with a molecular mass between 200 and 400 g/mol, and a polar surface area of about 50 Å2, and target DNA and/or topoisomerase as well as the cytoplasmic membrane. 8-Acetylnorchelerythrine, cryptolepine, 8-hydroxydihydrochelerythrine, 6-methoxydihydrosanguinarine, 2′-nortiliacorinine, pendulamine A and B, rhetsisine, sampangine, tiliacorine, tryptanthrin, tylophorinine, vallesamine, and viroallosecurinine yielded MIC ≤ 1 µg/mL and are candidates for the development of lead molecules.
... In Chinese medicine, the root tuber is used to stimulate muscles, detoxify the body, and expel intestinal gas, while its decoction is useful for treating rheumatoid arthritis, laryngitis, toothache, gingivitis, and intestinal and abdominal pain [43]. Several alkaloids [44][45][46][47][48][49][50][51], including coumarin, flavonoids, lignins, steroids, and terpenoids, have been identified in S. hernandifolia [52]. A survey among the local communities of North 24 Parganas, West Bengal, revealed that Stephania hernandifolia (Wild) Walp (Menispermaceae), locally known as Nimukho, is used to cure fever and to treat nerve, urinary, intestinal, and skin ailments. ...
Article
Full-text available
Stephania hernandifolia (Nimukho), an ethnomedicinal herb from rural Bengal, has been used traditionally for the management of nerve, skin, urinary, and digestive ailments. Here, we attempted to confirm the antiviral potential of aqueous, methanol, and chloroform extracts of S. hernandifolia against herpes simplex virus type 1 (HSV-1), the causative agent of orolabial herpes in humans, and decipher its underlying mechanism of action. The bioactive extract was standardized and characterized by gas chromatography-mass spectroscopy, while cytotoxicity and antiviral activity were evaluated by MTT and plaque reduction assay, respectively. Two HSV strains, HSV-1F and the clinical isolate VU-09, were inhibited by the chloroform extract (CE) with a median effective concentration (EC50) of 4.32 and 4.50 µg/ml respectively, with a selectivity index (SI) of 11. Time-of-addition assays showed that pre-treatment of virus-infected cells with the CE and its removal before infection reduced the number of plaques without lasting toxicity to the cell, indicating that the CE affected the early stage in the viral life cycle. The number of plaques was also reduced by direct inactivation of virions and by the addition of CE for a short time following attachment of virions. These results together suggest that modification of either the virion surface or the cell surface by the CE inhibits virus entry into the host cell. Graphic abstract
... In fact, it is well known that isoquinoline alkaloids are the main secondary metabolites of the genus Stephania. The chemical compositions and pharmacological properties of Stephania members have been reviewed (Semwal et al., 2010). This study described the isolation and structure identification of three new isoquinoline alkaloids (1, 3 and 4) and the 12 known compounds (2, 5-15) from the water soluble fraction of the methanol extract of the fresh tubers of this plant. ...
Article
Three new isoquinoline alkaloids, northalifoline 7-O-β-glucopyranoside (1), (R)-isococlaurine 4'-O-β-glucopyranoside (3) and (1R,3S)-1-(4-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (4) were isolated from the tubers of Stephania perriei in addition to 12 known compounds. The structure determinations were considered based on the spectroscopic evidence including 1D and 2D NMR and HR-ESI-MS experiments.
... In fact, it is well known that isoquinoline alkaloids are the main secondary metabolites of the genus Stephania. The chemical compositions and pharmacological properties of Stephania members have been reviewed (Semwal et al., 2010). This study described the isolation and structure identification of three new isoquinoline alkaloids (1, 3 and 4) and the 12 known compounds (2, 5-15) from the water soluble fraction of the methanol extract of the fresh tubers of this plant. ...
... The naturally occurring plants are an excellent source of various therapeutic substances. The obtained active ingredients from these plants were used as remedy to combat various ailments [1]. Euphorbia granulata Forssk. ...
Article
Full-text available
Background Naturally occurring substances of plant origin have long been used in folk medicine for curing various ailments including fever, pain, and inflammation etc. After careful evaluation on scientific bases, a large number of those substances provides cheaper alternative to currently used synthetic or semi-synthetic agents. Thus, with an aim of discovering alternative medicine for treatment of such ailments, current study was carried out. Euphorbia granulata Forssk. had long been used as a therapeutic agent against various morbid conditions, e.g., anthelmintic, snake bite, scorpion sting, purgative, and diuretic, and as blood purifying agent in folk medicine. The purpose of the current study was to determine the extended therapeutic use of Euphorbia granulata Forssk. based upon scientific evaluation, to explore the potential of its anti-proliferative, analgesic, antipyretic, and anti-inflammatory activities while using an aqueous methanol extract of the whole plant. Results In vivo study was performed on female rats of specie Rattus norvegicus weighing (100–150 g). Anti-inflammatory activity of the plant extract was calculated against using carrageenan induced paw edema. Analgesic potential both central and peripheral was assessed by using Eddy’s hot plate method and acetic acid-induced writhing model, respectively. The antipyretic potential was appraised using brewer’s yeast suspension, injected under the nape of the neck, and body temperature was measured using a digital thermometer. The plant extract strengths used for in vivo experiments were 50 mg, 100 mg, and 200 mg/kg (diluted in normal saline) and were administered through intra-peritoneal route. MTT assay was performed to estimate in vitro anti-proliferative potential. For this assay, a serial dilution of the plant extract was used with 100 μg/ml as the highest concentration. In vivo results demonstrated that plant extract at dose strength of 200 mg/kg, showed significant ( p * < 0.05) anti-inflammatory, analgesic, and antipyretic activities. In case of MTT assay, however, no significant anti-proliferative activity ( p > 0.05) was observed up to 100 μg/ml dose strength. Conclusion It can be concluded that aqueous methanol extract of Euphorbia granulata (whole plant) have shown significant anti-inflammatory, analgesic, and anti-pyretic activity in animal model. Therefore it can be a potential candidate, as a therapeutic alternative against treatment of algesia, pyrexia, and inflammation of various pathological origin. However, the plant extract did not demonstrate any significant anti-proliferation activity at doses used in this study.
... Protostephanine, an antihypertensive alkaloid, is present in the species under stud. [5][6][7] Flowering takes place during the month of May with the appearance of inflorescence of around 5-6.5 cm. ...
Article
Full-text available
Aims: Stephania japonica (Thunb.) Miers belonging to family Menispermaceae and is a highly demanded medicinal plant used in the name of Rajpatha for treatment of fever, malaria, jaundice, and various stomach disorders by the local traditional healers and pharmaceuticals for the preparation of medicines for related diseases. It is widely distributed in Northeastern India, i.e., Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura. Because of acute pressure on wild sources due to rapid exploitation and changing forest areas into agriculture land and various other developmental activities in a very short time, there will be the shortage of drug in the wild and needs to be cutivated this plants along with several others. Accordingly, a study has been carried out with the aim to develop easily accessible agro-technique for undertaking cultivation by the farmers in an easily accessible manner. Outcome of the study: This plant is a highly demanded medicinal plant distributed in North East India. Its cultivation is through tuberous root. Seeds also act as a tool for giving rise to new plants initiating from the mature viable seeds fallen on the ground. Seed germination is more accessible for this plant. The authors has developed various cultivation parameters in Regional Ayurveda Research Institute, Itanagar (Arunachal Pradesh) through seed germination and roots. Conclusion: Seeking out the practices of traditional use of tuberous root of S. japonica (Thunb.) Miers, there is an urgent need of cultivation. Accordingly, easily acceptable techniques for its cultivation is described in the present communication and cultivation can be made by establishing plant nurseries.
... Thirtyseven species of Stephania have been recorded from China (Luo et al. 2008). The plants of this genus are rich in alkaloids and are often used as pharmaceutical ingredients (Semwal et al. 2010). In this study, we sequenced and assembled the chloroplast genome of S. tetrandra for the first time. ...
Article
Full-text available
The complete chloroplast genome of Stephania tetrandra was sequenced and assembled for the first time. The chloroplast genome is 159,974 bp in length, containing a large single-copy (LSC) region of 90,539 bp and a small single-copy region (SSC) of 20,735 bp, separated by a pair of inverted repeats (IRs) of 24,350 bp. The genome contains 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. Among them, 15 genes have one intron each and three genes contain two introns. The overall GC content is 37.8%, while the corresponding values of LSC, SSC, and IR regions are 35.8, 32.4, and 43.7%, respectively. Phylogenetic analysis showed that S. tetrandra is more closely related to the clade of two species within Stephania, providing new insight into the evolution of Menispermaceae.
... It is widely used in the traditional treatment of various diseases e.g. asthma, tuberculosis, cancer, etc (Semwal et al., 2010). Reducing the fluidity of the membrane and therefore the drug resistance mechanisms, CEP intensifies the potency of anti-cancer agents, like Daunomycin, Vincristine and Adriamycin (Schiff, 1991;Shiraishi et al., 1987). ...
Article
Full-text available
Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid. Molecular dynamics studies show that CEP interacts with Voltage-dependent anion channel (VDAC), inducing the voltage-independent channel narrowing. In the new conformation, transport between mitochondria and cytoplasm is altered, which leads to the dose-dependent cytotoxicity. The biological effects of the interaction were investigated on glioblastoma multiforme (SNB-19) and neuronal (PC-12+NGF) cell lines. The cytotoxic potential of cepharanthine was determined by MTT assay and flow cytometry apoptosis/necrosis studies. T-type calcium channel and VDAC were labelled by the immunocytochemical method. Additionally, fluorescent labelling of reactive oxygen species and mitochondria was performed. Changes in the pore size of VDAC were calculated as well. Molecular dynamics simulations were carried out to examine the interactions of cepharanthine with VDAC. The obtained results prove that cepharanthine enhances the apoptosis in glioma and neuronal cells by the release of reactive oxygen species. Cepharanthine alters the mitochondria-to-cytoplasm transport and thus induces the cytotoxicity with no selectivity.
... This species is rich in IQAs, of which tetrandrine and fangchinoline are major constituents. These IQAs possess significant antimicrobial, antitumor, anti-inflammatory, and analgesic activities [4,5]. Although these metabolites are of wide pharmacological importance, their underlying biosynthetic pathways are still unclear. ...
Article
The roots of Stephania tetrandra are used as a traditional Chinese medicine. Isoquinoline alkaloids are considered to be the most important and effective components in this herb, but little is known about the molecular mechanism underlying their biosynthesis. In this context, this study aimed to reveal candidate genes related to isoquinoline alkaloid biosynthesis in S. tetrandra. Determination of tetrandrine and fangchinoline in the roots and leaves of S. tetrandra by HPLC showed that the roots had much higher contents of the two isoquinoline alkaloids than the leaves. Thus, a comparative transcriptome analysis of the two tissues was performed to uncover candidate genes involved in isoquinoline alkaloid biosynthesis. A total of 71 674 unigenes was obtained and 31 994 of these were assigned putative functions based on BLAST searches against 6 annotation databases. Among the 79 isoquinoline alkaloid-related unigenes, 51 were differentially expressed, with 42 and 9 genes upregulated and downregulated, respectively, when the roots were compared with the leaves. The upregulated differentially expressed genes were consistent with isoquinoline alkaloid accumulation in roots and thus were deemed key candidate genes for isoquinoline alkaloid biosynthesis in the roots. Moreover, the expression profiles of 10 isoquinoline alkaloid-related differentially expressed genes between roots and leaves were validated by quantitative real-time polymerase chain reaction, which indicated that our transcriptome and gene expression profiles were reliable. This study not only provides a valuable genomic resource for S. tetrandra but also proposes candidate genes involved in isoquinoline alkaloid biosynthesis and transcription factors related to the regulation of isoquinoline alkaloid biosynthesis. The results lay a foundation for further studies on isoquinoline alkaloid biosynthesis in this medicinal plant.
... It has been reported that natural remedies have a broad range of beneficial activities in the experimental studies [3][4][5][6][7][8][9][10]. Over the centuries, plant-based ailment has been used by different communities worldwide [11]. The local people of Bangladesh utilize medicinal plants as a primary source of their healthcare system to cure a large number of diseases [12]. ...
Article
Full-text available
Actinodaphne angustifolia Nees (Family: Lauraceae) is commonly used in folk medicine against urinary disorder and diabetes. The objective of the present study was to evaluate the antioxidant, cytotoxic, thrombolytic, and antidiarrheal activities of carbon tetrachloride (CCl4) fraction of leaves of A. angustifolia (CTFAA) in different experimental models. Antioxidant activity was evaluated by using qualitative and quantitative assays, while antidiarrheal effects assessed with castor oil-induced diarrheal models in mice. The clot lysis and brine shrimp lethality bioassay were used to investigate the thrombolytic and cytotoxic activities, respectively. CTFAA showed antioxidant effects in all qualitative and quantitative procedures. The fraction produced dose-dependent and significant (p<0.05 & p<0.01) activities in castor oil-induced diarrheal models. Moreover, CTFAA significantly (p<0.05) demonstrated a 15.29% clot lysis effect in the thrombolytic test, and the brine shrimp lethality assay LC50 value was 424.16 μg/ml bioassay. In conclusion, the current study showed CTFAA has significant antidiarrheal effects along with modest antioxidant and thrombolytic effects, and these data warrant further experiment to justify and include CTFAA as a supplement to mitigate the onset of diarrheal and cardiovascular disease.
... Plant derived medicine has tremendous efficacy as well as safe and cost effective. Therefore, traditional use of phytomedicine has been continuing for centuries around the world [1]. Traditional medicine has always played a pivotal role in the health care systems all over the world. ...
Article
Full-text available
The objective of this study was to evaluate the anti-diabetic and anti-diarrheal activity of methanol extract of Flemingia stricta Roxb. (Fabaceae) leaf. In anti-diabetic study, the extract was administered to alloxan-induce diabetic mice at two concentrations (200 mg/kg and 400 mg/kg body weight) for acute (12 hours) and prolong treatments (15 days) and blood glucose levels of diabetic mice were monitored at intervals of hours and days throughout the duration of treatment. Antidiarrheal test was conducted by castor oil induced diarrhea and enteropooling as well as intestinal motility in mice at three different concentration (100 mg/kg, 200 mg/kg and 400 mg/kg body weight). Treatment of alloxan induce diabetic mice with the extract caused a significant reduction in fasting blood glucose level of the diabetic mice both in acute (12 hours) and prolong treatment (15 days) and it was determined that the F. stricta methanol extract at both concentration (200 mg/kg and 400 mg/kg) showed the significant (P<0.05) hypoglycemic effect in comparison to the standard drug metformin. In the case of castor oil induced diarrheal test, enteropooling test and gastrointestinal motility test, the extract of F. stricta at 100 mg/kg, 200 mg/kg and 400 mg/kg has given significant effect (P<0.05) compared to the standard drug loperamide. But 400 mg/kg demonstrated the highest activity amongst the three doses. These results suggested that the methanol extract of F. stricta Roxb. possess promising anti-diabetic effect on alloxan-induced mice and significant antidiarrheal effect on castor oil induced diarrheal mice.
... Amongst the additional Fatty acids whose concentrations were found above 1% included: Palmitic acid (3.72%) in wild variety and (3.11%) in cultivated variety and Linoleic acid (2.06%) in wild variety. Rests of the fatty acids were having concentration amounts ˂1%.Oleic acid is vitalto normalize growth possessing active inhibition activity of the cyclooxiginase-2 catalyzed reaction leading to the biosynthesis of prostaglandin [22][23]. Obtained results showed that O.europaea seeds and fruitspossess various bioactive compounds like saturated and unsaturated fatty acids contain different pharmacological products. ...
Article
Full-text available
Olea europaea is medicinally valuable value in folk medicine. To determine components of derivatives of fatty acids were analyzed. Hyphenated technique of Gas chromatography utilized for this analysis. Results showed varieties of Olea europaea seed oil. Fatty acid methyl esters (FAMEs) Quantifications was done by using triplicat calibration curves compared with R2 > 0.99) in all cases. Oleic acid (C18:1c) was found at the highest amount of (9.87%) in wild variety and (8.86%) in cultivated variety which is essential for the normal growth and active inhibition activity of the cyclooxiginase-2catalyzed reaction leading to the biosynthesis of prostaglandin. Amongst the additional Fatty acids whose concentrations were found above 1% included: Palmitic acid (3.76%) in wild variety and (3.11%) in cultivated variety and Linoleic acid (2.06%) in wild variety. Remaining fatty acids were having concentrations less than 1%. Key words: Olea europaea; Fatty acids, Methylation, GC/MS,FAMES.
... Plant derived medicine has tremendous efficacy as well as safe and cost effective. Therefore, traditionally phytomedicine has been used for centuries around the world [1]. Traditional medicine has always played a pivotal role in the health care systems all over the world. ...
Preprint
Objective: To evaluate the anti-diabetic and anti-diarrheal activity of methanol extract of Flemingia stricta Roxb. (Fabaceae) leaf. Methods: In anti-diabetic study, the extract was administered to alloxan-induce diabetic mice at two concentrations (200mg/kg and 400mg/kg body weight) for acute (12 hours) and prolong treatments (15 days) and blood glucose levels (Blood glucose level) of diabetic mice were monitored at intervals of hours and days throughout the duration of treatment. Antidiarrheal test was conducted by castor oil induced diarrhea and enteropooling as well as intestinal motility in mice at three different concentration (100mg/kg, 200mg/kg and 400mg/kg body weight). Results: Treatment of alloxan induce diabetic mice with the extract caused a significant reduction in fasting blood glucose level of the diabetic mice both in acute (12 hours) and prolong treatment (15 days) and it was determined that the extract at both concentration (200mg/kg and 400mg/kg) showed the significant (P<0.05) hypoglycemic effect in comparison to the standard drug Metformin (10mg/kg). In the case of castor oil induced diarrheal test, enteropooling test and gastrointestinal motility test, the extract of F. stricta at 100mg/kg, 200mg/kg and 400mg/kg has given significant effect (P<0.05) in comparing to standard drug Loperamide (5mg/kg). Conclusion: These result suggested that the methanol extract of F. stricta Roxb. possess promising anti-diabetic effect on alloxan-induced mice and significant antidiarrheal effect on castor oil induced diarrheal mice.
... In South East Asian countries, this plant is traditionally used as tonic drug and medication for various diseases 10 . It was found that alkaloids are the main phytochemical compound of this genus 11 . Their biological activities have been reported including anti-cancer activity 12,13 , chemosensitizer 14 and acetylcholinesterase inhibition 15 . ...
Preprint
Full-text available
Naturally occurring phytochemical compounds have received considerable attention as alternative candidates for anti-amyloidogenic agents. This study, utilizing human insulin and amyloid beta peptide as an in vitro model, determined the anti-amyloid effects of alkaloids extracted derived from Stephania venosa. Alkaloids extracts including crebanine, O-methylbulbocapnine, tetrahydropalmatine and N-methyltetrahydropalmatine were used. Inhibition of amyloid protein aggregation were studied by fluorescence spectroscopy. Most alkaloids, except N-methyltetrahydropalmatine, exhibited the inhibitory properties against amyloid fibrillation either insulin or amyloid-beta peptide. Among alkaloids group, crebanine and tetrahydropalmatine showed the potent properties of anti-amyloidogenesis. These results suggest that alkaloids could be used as a natural compound for the development of drugs against amyloid protein aggregation for treatment of amyloid-related diseases.
... Rotundin nguồn gốc tự nhiên có những ưu điểm nổi bật như độc tính thấp, sự dung nạp thuốc tốt, mang lại giấc ngủ sinh lý, giúp hồi phục trí nhớ (L. T. Hung et al., 2010;Semwal et al., 2010;Thuy, Franke, Porzel, Wessjohann, & Sung, 2006). ...
Article
Củ bình vôi (Stephania rotunda Lour.) trồng tại tỉnh Hòa Bình được sử dụng làm nguyên liệu để chiết xuất l-tetrahydropalmatine (tên hoạt chất thuốc là Rotundin) C21H25NO4 - một alkaloid có tác dụng an thần, gây ngủ, giảm mất trí nhớ. Mục đích của nghiên cứu là tìm ra một quy trình chiết xuất rotudin đơn giản, rẻ tiền, hiệu quả để có thể ứng dụng. Kết quả thu được cho thấy: - Phương pháp ngâm chiết với tỉ lệ 1/6 giữa bột khô củ bình vôi và thể tích dung dịch H2SO4 1% cho hiệu suất trích ly cao nhất 0,35%. Hợp chất thu được đạt độ tinh khiết 98% (trên HPLC). - Cấu trúc hóa học được xác nhận trên phổ NMR.
... The interest of pharmaceutical industries has increased to discover the new drugs from the ethnobotanicals and also to provide new and alternative methods to synthetic drugs for the treatment of dreadful diseases. Stephania glabra belongs to Menispermaceae family, which includes 65 genera and 350 species (Semwal et al., 2010, Hong et al., 2015, Moongkarndi et al., 2004, Nakaoji et al., 1997, Montririttigri et al., 2008and Yang et al., 2010. S. glabra (Roxb.) ...
Article
Full-text available
Stephania glabra is a wild medicinal plant possessing multiple uses as anti-cancer, antimicrobial and antioxidant activities. Different extracts and fractions were prepared from S. glabra tubers and were analyzed for different activities. Evaluation of the total phenolic and flavonoid content revealed that chloroform extract of S. glabra contain maximum phenolic content and maximum flavonoid content was found in methanolic extract. Dry powder analysis of the tubers revealed the presence of saponins, alkaloids and proteins. Ethyl acetate extract of S. glabra tubers showed highest antioxidant potential as revealed by ABTS radical scavenging activity. Methanolic extract has the highest anti-cancer activity while chloroform extracts and fractions have highest antimicrobial activity. These activities can be attributed to the high amount of the phytoconstituents present in these extracts
... Detailed information about their botany, distribution, medicinal uses, plant parts used, dosage, administration, phytochemical constituents, biological activities and toxicological properties are documented in the monograph entitled "plant resources of tropical Africa 11: medicinal plants 1" (de Ruijter 2008a-c). Some members of the Menispermaceae family are used as traditional medicines against diseases and ailments such as gastro-intestinal problems, ear, eye, blood circulatory problems, musculoskeletal, neurological, psychological, respiratory infections, skin problems, urology and reproductive health problems (De Wet & Van Wyk 2008, Jahan et al. 2010, Kumar et al. 2010, Meenu & Radhakrishnan 2020. Moreover, some species are characterized by many types of alkaloids, particularly the bisbenzylisoquinoline alkaloids which are derived from the benzyltetrahydroisoquinoline skeleton (Menachery 1996, Otshudi et al. 2005, Meenu & Radhakrishnan 2020. ...
... The species used in TCS namely Clematis simensis (Tadele 2017), Jasminum abyssinicum (Tadiwos et al. 2017), Jatropha curcas (Abdelgadir and Van Staden 2013;Cavalcante et al. 2020), Olea europaea (Ali et al. 2015), Salvadora persica (Ahmad and Rajagopal 2013;Niazi et al. 2016;Zakariyyah et al. 2017;Khan et al. 2020), Schinus molle (Hosni et al. 2020), Stephania spp. (Kumar et al. 2010), and Tribulus terrestris (Vadakkan et al. 2018) reported analgesic effect. Plant species used in the chew and hold method for relieving pains are also known for the same effect. ...
Chapter
Oral health is known to be associated with overall health and contributes to physical fitness and performances. It also has significant impacts on the quality of daily life. The traditional chewing sticks (TCS) obtained from different plant species are commonly used in the African continent and other neighboring countries. Salvadora persica, Vernonia amygdalina, Acacia nilotica, and Clausea anisata are among the most commonly used plant species for making chewing sticks. Plant parts such as twigs, roots, and stems are mainly used as TCS and are also reported to have antimicrobial, antioxidant, anti-inflammatory, and antiseptic activities. Additionally, they are attributed to its mechanical action to remove caries (decays), plaque, etc., and thus play an important role in keeping oral hygiene in good condition. This chapter provides an overview of the role of TCS in oral hygiene in Africa and elsewhere and its phytochemical investigations. For the effective utilization of the pharmacological potentials of TCS, it is important to understand the overall phytochemistry of the TCS. Both validating the traditional knowledge from ethnobotanical studies and justification for the chemical effect of using TCS are the driving forces for further phytochemical investigations.
... The inhibition of AG has been studied in the five plants used for the treatment of diabetes. Twenty-one compounds derived from A. paniculate [45,46,47,48,49], 16 compounds derived from C. verum [50,51,52], 11 compounds derived from S. suberosa [53,54], 9 compounds derived from T. crispa L [55,56,57], and 4 compounds derived from T. laurifolia [58,59] were docked into the AG target site AG with ArgusLab. Docking effects were considered when the binding energy values were less than those of acabose-AG. ...
Article
Full-text available
The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC50). In vitro experiments showed that crude Cinnamomum verum extract (IC50=0.35±0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC50=0.69±0.39 mg/mL), Stephania suberosa (IC50= 1.50±0.17 mg/mL), Andrographis paniculate (IC50 = 1.78±0.35 mg/mL), and Thunbergia laurifolia (IC50 = 4.66±0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC50= 0.55±0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC50 =819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC50 =4.46 nM, 6 HIs); ergosterol peroxide (IC50 =4.18 nM, 6 HIs); borapetoside D (IC50 =508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC50 =1.09 nM, 2 HBs and 2 His), stephasubimine (IC50 =285.37 pM, 6 HIs); and stephasubine (IC50 =1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.
... The genus Stephania (Menispermaceae) has long been used in traditional medicine to treat various ailments (Semwal et al. 2010). Stephania pierrei Diels, also known as Sabu-lueat in Thai (Intusaitrakul 2010), is a common traditional herb in South-East Asia (Dary et al. 2015) whose tubers are used as an ayurvedic herb, health tonic, analgesic, skeletal muscle relaxant, and treatment for diseases including cancer, diabetes, migraines, postpartum haemorrhage, leucorrhoea, and anaemia (Tantisewie and Ruchirawat 1992;Intusaitrakul 2010). ...
Article
Full-text available
Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E2, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.
... Rotundin nguồn gốc tự nhiên có những ưu điểm nổi bật như độc tính thấp, sự dung nạp thuốc tốt, mang lại giấc ngủ sinh lý, giúp hồi phục trí nhớ (L. T. Hung et al., 2010;Semwal et al., 2010;Thuy, Franke, Porzel, Wessjohann, & Sung, 2006). ...
Article
Tubers of Stephania rotunda Lour. grown in Hoa Binh province are used as raw materials for extracting l-tetrahydropalmatine (a medical jargon-Rotundin) C21H25NO4 - a major component - alkaloid with the effects of sedative and preventing loss of memory. The purpose of this research is to study a simple, inexpensive, and efficient procedure for extracting rotudin. - Maceration method of 1/6 of dried powder of tubers with 1% H2SO4 solution gives the highest yield of 0.35% on the extraction. The purity of rotudin is 98% on HPLC. - The chemical structure of rotudin was confirmed by NMR data.
... However, the effects of the internal active ingredients of S. hainanensis as a medicinal plant are still uncertain. Stephania hainanensis alkaloids (SHAs) have many pharmacological activities, such as sedative and anti-addictive actions and anti-inflammatory effects [14]. The analgesic and anti-inflammatory effects of SHA have also been confirmed in experiments with animal models, such as the hot-plate test, acetic acid-induced twisting reaction, and dimethylbenzene-induced ear swelling in mice [15]. ...
Article
Full-text available
Background Gout is initiated by the precipitation of monosodium urate (MSU) crystals within the joints and soft tissues, and it can eventually cause acute or chronic arthritis. MSU crystals trigger, amplify, and maintain a strong inflammatory response through promoting proinflammatory activity. In this study, the therapeutic effects of Stephania hainanensis (S. hainanensis) total alkaloid (SHA) were tested and evaluated on MSU-induced acute gouty arthritis in a mouse model. Methods After oral administration of SHA (10 or 20 mg/kg) or the antigout medicine colchicine (0.5 mg/kg) once daily for 3 consecutive days, MSU crystals suspended in saline (2.5 mg/50 μl) were intradermally injected into the right paw of the mice. Then, SHA and colchicine were administered for another 2 days. During this period, swelling of the ankle and clinical scores were measured at 12, 24, and 48 h postinjection. After the mice were euthanized, inflammatory cytokine expression and paw tissue inflammation-related gene and protein expression, and a histopathological analysis was performed. Results SHA had obvious therapeutic effects on MSU-induced acute gouty arthritis in mice. SHA alleviated ankle swelling and inhibited the production of cytokines, such as IL-1β and TNF-α. In addition, NLRP3, Caspase-1 and IL-1β, which are activated by MSU were also suppressed by SHA. The histological evaluation showed that SHA relieved the infiltration of inflammation around the ankle. Conclusions These results suggest that SHA is capable of anti-inflammatory activities and may be useful for treating gouty arthritis.
... Cepharanthine is an active alkaloid isolated from Stephania cepharantha Hayata (Semwal et al., 2010). In Japan, Cepharanthine has a history of more than 70 years in treating radiation-related leukopenia (Kanamori et al., 2016), venomous snakebites (Hifumi et al., 2013), alopecia areata (Hon and Leung, 2011) and other pathologies. ...
Article
Full-text available
Cepharanthine (CEP) is an active alkaloid isolated from Stephania Cepharantha Hayata. It is reported that the anti‐inflammatory properties of CEP could be employed to treat a variety of diseases. In this study, we first found that CEP ameliorates ulcerative colitis (UC) induced by DSS. The effect of CEP on gut microbiota was further evaluated by 16S rRNA gene sequencing, antibiotic pretreatment and faecal microbiota transplantation (FMT). Results showed that the abundances of gut microbiota, such as Romboutsia, Turicibacter and Escherichia‐Shigella (especially Romboutsia), were significantly reduced after CEP treatment. Additionally, we explored the mechanisms of CEP by a strategy integrating transcriptomics with network pharmacology. The transcriptome data confirmed that CEP functioned through cytokine and cytokine receptor pathways. The expression levels of 10 pro‐inflammatory hub genes (such as CXCL1, CXCL9, CCL7) were positively correlated with the abundance of Romboutsia. Our data identified Romboutsia as a potential pathobiont in UC. Collectively, we confirmed that CEP relieved colon inflammation by modulating gut microbiota and pro‐inflammatory cytokine expression. CEP can be adopted to design novel effective therapeutic strategies for UC. We confirmed that Cepharanthine relieved colon inflammation by modulating gut microbiota and pro‐inflammatory cytokine expression. Cepharanthine can be adopted to design novel effective therapeutic strategies for UC.
... It has been widely applied to therapy of rheumatoid arthritis, rheumatism, edema, and hypertension (Jiang et al., 2020). Modern pharmacological studies have shown that it exhibits wide pharmacological activities, including anti-tumor, anti-inflammatory, neuroprotective, and antiviral effects (Semwal et al., 2010;Jiang et al., 2020;Zhang et al., 2020a). Previous chemical March 2022 | Volume 13 | Article 874583 Li et al. ...
Article
Full-text available
Stephania tetrandra (S. Moore) is a source of traditional Chinese medicine that is widely used to treat rheumatism, rheumatoid arthritis, edema, and hypertension. Benzylisoquinoline alkaloids (BIAs) are the main bioactive compounds. However, the current understanding of the biosynthesis of BIAs in S. tetrandra is poor. Metabolite and transcriptomic analyses of the stem, leaf, xylem, and epidermis of S. tetrandra were performed to identify candidate genes associated with BIAs biosynthesis. According to the metabolite analysis, the majority of the BIAs accumulated in the root, especially in the epidermis. Transcriptome sequencing revealed a total of 113,338 unigenes that were generated by de novo assembly. Among them, 79,638 unigenes were successfully annotated, and 42 candidate structural genes associated with 15 steps of BIA biosynthesis identified. Additionally, a new (S)-norcoclaurine-6-O-methyltransferase (6OMT) gene was identified in S. tetrandra, named St6OMT2. Recombinant St6OMT2 catalyzed (S)-norcoclaurine methylation to form (S)-coclaurine in vitro. Maximum activity of St6OMT2 was determined at 30°C and pH 6.0 in NaAc-HAc buffer. Its half-life at 50°C was 22 min with the Km and kcat of 28.2 μM and 1.5 s−1, respectively. Our results provide crucial transcriptome information for S. tetrandra, shedding light on the understanding of BIAs biosynthesis and further gene functional characterization.
... There is no mention of the medicinal uses in Thai traditional medicine, and the chemical constituents of this species have not been carried out. In fact, it is well known that members of this genus contain isoquinoline alkaloids as major constituents (Semwal et al., 2010). From our previous phytochemical investigation of the related species S. pierrei, we also reported the isoquinoline alkaloids (Maliwong et al., 2021). ...
Article
Two isomers of megastigmane glycosides, (6R, 9S)-blumenol C 9-O-gentibioside (2) and (6S, 9S)-blumenol C 9-O-gentiobioside (3), and a new 7,9′-dinorlignan glycoside, stepdonorlignoside (4) were isolated from the tubers of Stephania kaweesakii. The structure determinations were considered based on the physical data and spectroscopic evidence. The absolute configurations of two megastigmanes were determined for the first time. Additionally, ten known compounds were isolated: (6R, 9S)-blumenol C 9-O-β-D-glucopyranoside, (+)-isolariciresinol 3a-O-β-D-glucopyranoside, salidroside, N-trans-caffeoyltyramine, (R)-isococlaurine, (R)-isococlaurine 4′-O-β-glucopyranoside, (−)-oblongine, (+)-magnocurarine, fordianoside, and (−)-cyclanoline.
Article
Aim Validation of antiviral activity of Stephania hernandifolia against HSV-2. Background Ethnomedicinal plant Stephania hernandifolia, traditionally used for the management of skin, digestive and nerve ailments demonstrated significant anti-HSV-1 activity; similar to Stephania cepharantha having neuroinflammatory and anti-HSV activities. Objectives Thus, the present study was aimed to validate the potential of the most active fraction-2 (F-2) of S. hernandifolia against HSV-2 in vitro, along with the underlying mode or mechanism of action. Methods The standardized F-2 was characterized by GC-MS, 1H-NMR, Mass and FTIR spectroscopy. Cytotoxicity (CC50) and antiviral activity (EC50) was evaluated by MTT and Plaque reduction assay. To determine the mode of action, we have used time-of-addition, virus inactivation, and entry (attachment and penetration) assays, followed by semiquantitative PCR. Furthermore, the protein expression levels of immediate early (IE) and early (E) gene products of drug-treated virions were measured by Western blot. Results The results showed that HSV-2G and ICMR/VU-2012/20, the clinical isolate of HSV-2, were inhibited by F-2 at EC50 of 20.0 and 20.43 µg/ml respectively, with Selectivity Index (SI) of 12. Time-of-addition assay showed that F-2 significantly inhibited HSV-2 infection in Vero cells at 4-8 h post-treatment. The infectivity of the virion was lost within 1h of exposure to F-2 (EC50 and EC99). Furthermore, semi-Q-PCR, and Western blot studies demonstrated significant downregulation of IE and E gene products. The characterization revealed that 2-chloroethyl linoleate is the lead compound in the F-2 fraction. Conclusion Thus, our results showed that the bioactive fraction F-2, inhibits both IE and E transcription of HSV-2.
Article
Rhizophora apiculata is a less studied tannin-rich plant of the mangrove ecosystem with potent biomedical applications. Tannins have been known to reduce silver ions into silver nanoparticles which in particular are known to possess cytotoxic effects against a variety of cancer cells. The aqueous leaf extract was prepared and quantitatively analyzed for its phytochemical content. According to the quantitative phytochemical analysis, the extract was rich in tannins and other reducing sugars. The reducing sugar-rich extract was further used for the synthesis of silver nanoparticles. Taking these facts into consideration, in this study, an eco-friendly approach was followed to biosynthesize silver nanoparticles using a tannin-rich Rhizophora apiculata aqueous leaf extract. The synthesized nanoparticles were partially characterized by our previous reports. This report further characterizes the particles by determining its average size, polydispersity index and zeta potential using dynamic light scattering. After characterization, the nanoparticles were tested for cytotoxic effects against human osteosarcoma MG-63 cells. The effects were analyzed by microscopic observation and MTT assay. The results indicate that the tannin-rich extract reduced the precursor silver nitrate into silver nanoparticles of favorable size for tumor infiltration. The nanoparticles possessed significant cytotoxic effects against MG-63 cells which could be possibly attributed to the antioxidant activity of silver nanoparticles. Further studies at the molecular level can indicate its potential in nanomedicine for the treatment of bone cancer at the clinical level.
Article
Three new hasubanan-type alkaloids, stephalonine Q (1), stephalonine R (2) and stephalonine S (3), together with four known alkaloids, isolonganone (4), eletefine (5), aurantiamide (6), N-cinnamoyltyramine (7), were isolated from the whole plant of Stephania longa. Their structures were identified by NMR, HR-ESI-MS, CD methods and x-ray crystallography, as well as by comparison with the literature data. All isolated compounds were evaluated for their antimicrobial activities against five bacteria in vitro. Compound 5 displayed inhibitory activity against only S. aureus, with an MIC value of 50 μg/mL.
Article
Ethnopharmacological relevance the root of Stephania tetrandra S. Moore, known as Fangji in China (Chinese: 防己), is a traditional Chinese medicine (TCM) with a long history of use. Fangji is a type of medicine used to treat various diseases, including rheumatism, arthralgia, edema and beriberi, unfavorable urination, and eczema. Aim of this review There are many newly published reports on the history of uses, phytochemistry, pharmacological activity, quality control and toxicity of Fangji; however, no comprehensive systematic review exists. Therefore, the purpose of this review is to compile the latest and most comprehensive information on Fangji and provide a scientific basis for future research. Materials and methods A systematic literature search was conducted using multiple electronic databases, including SciFinder, Web of Science, PubMed, Science Direct, ACS Publications, J-stage, SpringerLink, Thieme, Wiley, and CNKI. Information was also collected from journals and Chinese Pharmacopoeia. Result Thus far, there were uses of Fangji against 20 different diseases/disorders, such as relieving edema and rheumatism pain, treating cough and asthma, treating enuresis, astringent urine and beriberi edema, purging blood and damp heat, and dispelling wind evil and dampness, etc. 48 compounds have been isolated from Fangji, belonging to alkaloids, flavonoids, and steroids, other compounds. The crude extracts and isolated compound of Fangji have shown a wide range of pharmacological activities, such as anti-tumor, anti-inflammatory, and neuroprotective activities, as well as role in reoxygenation, and antimicrobial effect, etc. Moreover, qualitative and quantitative analyses of quality control are reviewed, including qualitative analyses for the identification of compounds, as well as fingerprint and quantitative analyses by high performance liquid chromatography (HPLC) and capillary electrochromatography (CE). In the toxicity study, the hepatotoxicity, hepatorenal toxicity, nephrotoxicity, subacute and acute toxicities of the alcohol extract and water extract of Fangji, and tetrandrine were studied in-vitro and in-vivo experiments. Conclusion In the history of uses, Fangji can be used to treat a variety of diseases, most of which are manifested in removing wind and dampness. In recent years, the phytochemistry of Fangji has rarely been reported. The pharmacological activities of Fangji mainly focus on the compounds, tetrandrine and fangchinoline, and there are a few reports on the pharmacological studies of other compounds in Fangji. Moreover, the quality control of Fangji lacks a standard fingerprint to distinguish Fangji from other easily-confused medicinal materials. In the toxicity study, there is no report on the mechanism of toxicity research. Therefore, further studies on such mechanisms are needed.
Article
Full-text available
Pendataan flora di Cagar Alam Gunung Tilu Bandung Jawa Barat masih terbatas. Di sisi lain, eksploitasi tumbuhan menjadi ancaman terhadap penurunan flora yang mengakibatkan rawan kepunahan. Penelitian ini difokuskan pada pendataan jenis tumbuhan berbiji di kawasan tersebut. Pengambilan data dilakukan di zona pegunungan Cagar Alam Gunung Tilu, Bandung, Jawa Barat, untuk mengungkap keanekaragaman spesies di kawasan tersebut. Pengumpulan data dilakukan dengan metode survei di blok Malagembol, pada ketinggian 1.500 - 2.100 mdpl. Pendataan jenis meliputi nama daerah dan nama ilmiah, sedangkan data morfologi dicatat dalam buku lapangan dan difoto. Sampel yang belum teridentifikasi dijadikan sebagai voucer herbarium untuk diidentifikasi lebih lanjut. Status konservasi tumbuhan dicatat berdasarkan pangkalan data IUCN redlist. Studi pustaka dilakukan untuk melengkapi data biopotensinya. Sebanyak 74 suku, 178 marga dan 260 jenis dicatat pada area pengamatan. Hasil temuan pada penelitian ini dapat dijadikan acuan dalam rencana pengelolaan hutan untuk menentukan spesies prioritas untuk dikonservasi. Data tumbuhan endemik dan terancam yang tercatat dari daerah penelitian dapat digunakan lebih lanjut untuk memastikan bahwa daerah tersebut tetap terlindungi dan lestari serta digunakan untuk tujuan konservasi dan penelitian.
Article
This review critically summarized the synthesis of hasubanan alkaloids with the focus on construction of hasubanan core. Historical and recent reports are systemized based on the strategic bonds formation and are given in comparison. Special accents are made on the achievements in collective syntheses, asymmetric syntheses, and biomimetic approaches. Based on the summarized data potential perspectives are highlighted. This review outlines challenges and perspectives in total synthesis of hasubanan alkaloids with highlight on collective and biomimetic approaches. Providing historical background and comparison of the methods helps to outline current achievements in the area.
Article
Full-text available
Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.
Article
Ethnopharmacological relevance Approximately 60 species of the genus Stephania (Menispermaceae) are distributed worldwide. Among these, 39 species are located in South and Southwest China; in particular, these plants are rich in alkaloids and were used in traditional Chinese medicine (TCM) against numerous ailments. Aim of this review The purpose of this study was to provide organized information on the ethnopharmacological uses as well as the phytochemical, pharmacological, and toxicological evaluation of the alkaloids derived from plant species included in the genus Stephania. In addition, we aimed to provide comprehensive basic knowledge on the medicinal properties of these plants and establish meaningful guidelines for further research. Materials and methods Information related to the Stephania genus was collected from scientific databases, such as Web of Science, PubMed, Baidu Scholar, and China Academic Journals (CNKI), within the last 20 years on phytochemistry, pharmacology, and toxicology of the plants in genus Stephania. Furthermore, information was obtained from the Pharmacopoeia of the People's Republic of China. Chinese Pharmacopoeia and Flora of China. Results Plant species belonging to the genus Stephania have been mentioned as traditional remedies and various alkaloidal compounds have been identified and isolated, including aporphine, proaporphine, morphinane, hasubanane, protoberberine, benzylisoquinoline, and bisbenzylisoquinoline and among others. The isolated alkaloidal compounds reportedly exhibited promising pharmacological properties, such as antimicrobial, antiviral, antitumor, antioxidant, antihyperglycemic, anti-inflammatory, antinociceptive, anti-multidrug resistance, neuroprotective, and cardioprotective activities. Conclusions The genus Stephania is widely used in TCM. The ethnopharmacological uses, phytochemistry, and pharmacology of the Stephania sp. Described in this review demonstrated that these plants contain numerous alkaloids and active constituents and display myriad pharmacological activities. Typically, research on the plants’ pharmacological activity focuses on parts of the plants and the associated compounds. However, many Stephania species have rarely been studied, and the ethnomedicinal potential of those discovered has not been scientifically evaluated and needs to be further elucidated. Furthermore, quality control and toxicology studies are warranted in the future.
Article
Full-text available
Natural products are great treasure troves for the discovery of bioactive components. Current bioassay guided fractionation for identification of bioactive components is time- and workload-consuming. In this study, we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay. As a proof-of-concept, the strategy was applied to identify angiotensin converting enzyme (ACE) inhibitors of Fangjihuangqi Decoction (FJHQD), a traditional medicine clinically used for the treatment of heart failure. The chemical profile of FJHQD was comprehensively revealed with the assist of tandem mass spectral molecular networking, and a total of 165 compounds were identified. With characterized constituents, potential clinical applications of FJHQD were predicted by Batman-TCM, and a range of cardiovascular related diseases were significantly enriched. ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe. FJHQD exhibited excellent ACE inhibitory effects, and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD. This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities, which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma, saponins from Astragali Radix, and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma, were principal components responsive for this effect of FJHQD. Among them, four novel ACE inhibitors were firstly reported. Our study indicated that the proposed strategy offered a useful approach for uncovering the bioactive profile of traditional medicines and provided a pragmatic workflow for exploring bioactive components.
Article
Background Cepharanthine (CEP), which is extracted from Stephania cephalantha, is commonly prescribed to treat alopecia areata; however, the scientific evidence for its efficacy is limited. Objective To investigate the effect of CEP and its structural analogues on human hair growth in vitro. Methods The effects of CEP and three structural analogues of CEP on the proliferation of human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs) were investigated. Their effects on vascular endothelial growth factor (VEGF) expression were also assessed by real‐time PCR. Finally, the activation of pathways leading to VEGF expression, such as intracellular Ca²⁺ mobilization and hypoxia‐inducible factor (HIF) expression, was characterized. Results CEP and two structural analogues of CEP significantly stimulated the growth of hDPCs but not hORSCs. Moreover, CEP and all three structural analogues significantly induced the expression of VEGF in hDPCs. CEP increased the intracellular Ca²⁺ concentration in hDPCs. CEP also increased the expression of HIF‐1α and HIF‐2α and induced the expression of HIF‐responsive genes in hDPCs, even under normoxia. Conclusions These results suggest that CEP and its structural analogues have the potential to restore hair growth by promoting the proliferation of hDPCs and increasing their expression of VEGF.
Article
Stephania epigaea H. S. Lo is a folk medicine widely distributed in the south of China, especially in Yunnan and Guangxi province. An in vitro anti-neuroinflammatory study showed that total alkaloids of it can potently inhibit LPS-induced NO releasing of BV2 cells with an IC50 value of 10.05 ± 2.03 μg/mL (minocycline as the positive drug, IC50 15.49 ± 2.14 μM). The phytochemical investigation of the total alkaloids afforded three new phenanthrene (1-3), two lactams (4a, 4b), and nine aporphine derivatives (5-13). The final structure of 1 was identified by computer-assisted structure elucidation (ACD/Structure Elucidator software and the ¹³C NMR calculation with GIAO method) due to many possibilities of the substituent pattern. All isolates were evaluated for their anti-neuroinflammatory effects, and as a result, 5, 8, 10, and 11 exhibited stronger inhibitory activities than the minocycline. The results suggested S. epigaea could provide potential therapeutic agents for neurodegenerative diseases.
Article
Tetrandrine (TET) and fangchinoline (FAN) are dominant bisbenzylisoquinoline (BBIQ) alkaloids from the roots of Stephania tetrandra of the family Menispermaceae. BBIQ alkaloids comprise two benzylisoquinoline units linked by oxygen bridges. The molecular structures of TET and FAN are exactly the same, except that TET has a methoxy (−OCH3) group, while FAN has a hydroxyl (−OH) group at C7. In this overview, the current knowledge on the chemistry, pharmacology and anticancer properties of TET and FAN have been updated. The focus is on colon and breast cancer cells, because they are most susceptible to TET and FAN, respectively. Against colon cancer cells, TET inhibits cell proliferation and tumor growth by inducing apoptosis and G1 cell cycle arrest, and suppresses adhesion, migration and invasion of cells. Against breast cancer cells, FAN inhibits cell proliferation by inducing apoptosis, G1-phase cell cycle arrest and inhibits cell migration. The processes involve various molecular mechanisms and signaling pathways. Some insights on the ability of TET and FAN to reverse multi-drug resistance in cancer cells and suggestions for future research are provided. Please cite this article as: Chan EWC, Wong SK, Chan HT. An overview on the chemistry, pharmacology and anticancer properties of tetrandrine and fangchinoline (alkaloids) from Stephania tetrandra roots. J Integr Med. 2020; Epub ahead of print.
Article
We report the first enantioselective total syntheses of the hasubanan alkaloid (-)-metaphanine and the norhasubanan alkaloid (+)-stephadiamine. Key features of these syntheses include diastereoselective oxidative phenolic coupling reaction and subsequent regioselective intramolecular aza-Michael reaction, which efficiently construct the hasubanan skeleton with the all-carbon quaternary stereogenic center at C13. Based on our hypothesis regarding the biosynthetic pathway of (+)-stephadiamine, we found that (-)-metaphanine is easily converted to (+)-stephadiamine via aza-benzilic acid type rearrangement reaction.
Article
Full-text available
In this study, methanolic crude extracts of Stephania japonica (Thunb.) Miers. (MESJ) whole plants were examined for possible antidepressant and sedative-hypnotic activities. Herein, the forced swimming test and tail suspension test were conducted to explore the antidepressant activity. In addition, the open field test and hole-board test were performed to evaluate the sedative-hypnotic activities. In the acute toxicity test, the MESJ ensured safety up to a dose of 2000 mg/kg, p.o. The experimental doses were 100 and 200 mg/kg p.o. In both the forced swimming test and tail suspension test, the extract significantly (p<0.01 and p<0.05) inhibited immobility time in a dose dependent manner compared to the control. These results (13.56-26.46% inhibition) indicate the mild antidepressant activity of MESJ compared to nortriptyline (60.4-64.6% inhibition). The open field test and hole-board test demonstrated the dose dependent significant (p<0.001, p<0.01 and p<0.05) and moderate sedative-hypnotic activities of the extract compared to diazepam. However, these activities were found to gradually decrease after 60 min in the open field test and must be considered as short-term activities, compared to diazepam. It can be claimed that the methanolic crude extract of Stephania japonica possesses mild antidepressant and moderate but short-term sedative-hypnotic activities.
Article
Full-text available
Chemical investigation of the EtOH extract from the tubers of Stephania succifera collected in Hainan Province of China resulted in the isolation of the two new alkaloids Cepharanone D (1) and N-formyl-asimilobine (2), and a known alkaloid, N-formyl-annonain (3). Their structures were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR). The antimicrobial activities of the three compounds were also investigated.
Article
Full-text available
Stephania venosa is a plant rich of alkaloids of family Menispermaceae. In Thailand, the study on this plant revealed a wild variety of phytochemical constituents. Those including flavonoids, alkaloids, terpenoids, sulfides, and polyphenolics. In this study, we analyzed the anticancer activity according to the antiproliferation and apoptotic activity of the pure constituent isolated from S. venosa tuber on human ovarian cancer cells (SKOV3). During phytochemical processes, we concomitantly tested the activity of the isolates and selected the effective fractions for further purification. Crude ethanolic extract and pure constituent were obtained from the tuber of S. venosa and evaluated the cytotoxic activity against SKOV3 by MTT assay. Crude ethanolic extract was performed various fractionations and further isolated to obtain pure constituent. Purified constituent and crude extract were demonstrated the significant effect on antiproliferation in a dose dependent manner. Apoptotic effect was confirmed by morphological changes, DNA fragmentation and caspase activation assay. The cytotoxic activity of crude ethanolic extract showed a potent inhibition with an ED 50 value at 31 μg/ml. Structure of the pure constituent was determined by NMR technique and identified as aporphine. Aporphine from S. venosa showed the antiproliferation at ED 50 value at 6 μg/ml against SKOV3. Results from the morphological changes, DNA fragmentation and caspase activation assay, in this study demonstrated that aporphine could significantly inhibit the treated tumor cell proliferation and cause cells death via apoptosis, whereas those were not found in the untreated cells. We concluded that the pure constituent from S. venosa could lead to the further study on the detail mechanisms of action of this active substance for future application as new drug for ovarian cancer. ©All right reserved.
Article
Full-text available
Stephania venosa (Bl.) Spreng (S. venosa) is a Thai medicinal plant locally known as "Saboo luad" or "Boraphet plungchang". It was used for treating various illnesses including cancer. This study aimed to investigate cytotoxic activity of the water extract from S. venosa tubers on human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy subjects were used to examine cytotoxic effect of the extract by using trypan blue dye exclusion method. The results demonstrated cytotoxic activity of the extract with its IC 50 at 300 mg/mL. The effect of the extract on apoptotic induction was also evaluated at the concentration of 300 mg/mL on PMBCs from healthy subjects and from cervical cancer patients by using the terminal deoxynucleotidyl transferase (TUNEL) assay. The results revealed that the extract significantly induced apoptosis of the PBMCs from both healthy subjects and from the patients, similar to 60 Co radiation at 0.5 Gy, when compared to the untreated cells. The additive effect on apoptosis induction was also observed when the extract was used in combination with 60 Co radiation to treat the PBMCs from healthy subjects. We also studied the antiproliferative effect of the extract on the cells from healthy subjects by using by 3 H-thymidine incorporation assay. It was demonstrated that the extract had antiproliferative activity with IC 50 at 40 mg/ mL. Taken together, these results suggest that the water extract of S. venosa tubers possess antitumor potential via cytotoxic, apoptotic and anti-proliferative properties.
Article
Full-text available
The title compound, C21H25NO4 .H2O, was isolated from the rhizome of Stefania rotunda L. of Vietnam and its structure elucidated. An S configuration was found at the asymmetric C13 atom of the (-)-enantiomer. The water molecule generates infinite helically arranged molecular columns around the screw axes in the z direction through intermolecular hydrogen bonds.
Article
From the root tuber of Stephania rotunda LOUREIRO, (-)-tetrahydropalmatine (I) and stepharine (IIa) were isolated together with a new phenolic base of tetrahydroprotoberberine type, stepharotine (hydrobromide, m.p. 227∼229°, [α]³⁴D-203°(MeOH), C31H25O5N·HBr). The structure of O-methylstepharotine (m.p. 133∼135°, [α]³⁵D -270°(CHCl3), C22H27-O5N) was identified by comparison with the synthesized 2, 3, 9, 10, 11-pentamethoxytetra-hydroprotoberberine (VI a). The mass spectrum of stepharotine trideutero-O-methyl ether (VI b), revealed that the phenolic hydroxyl in stepharotine is present in either 9-, 10-, or 11-position. Cleavage reaction of stepharotine O-phenyl ether (VI c) with metallic sodium in liquid ammonia gave (-)-tetrahydropalmatine (I) and (-)-tetrahydropalmatrubine (V c). These experiments revealed that stepharotine is represented by formula III.
Article
A novel skeleton alkaloid, excentricine, was isolated from the roots of stephaniaexcentrica. The recent introduced selective long - range DEPT and 1D multiple relay COSY NMR techniques have been successfully used to identify and to connect spin systems separated by quaternary carbons and heterotoms and total assignment of 1H and 13C NMR spectra were achived. Its structure has been elucidated as 1.
Article
Aim: To study the alkaloids of Stephania epigaea Lo and their cytotoxicities against several cancer cell lines. Methods: Alkaloids were isolated by column chromatography and their structures were elucidated by spectroscopic analysis. Results: Six known alkaloids including (+)-cepharanthine (1), cycleanine (2), (-)-norcycleanine (3), isochondodendrine (4), delavaine (5) and runanine (6) were isolated from the plant. Conclusion: Alkaloids 3-6 were first isolated from the plant. Alkaloid 1 exhibited potent cytotoxicities against Ramos, A549, and P388 cell lines. Alkaloids 2-4 showed potent cytotoxicities against Ramos cells.
Article
Four new bisbenzylisoquinoline alkaloids named fenfangjines A, B, C, and D were isolated from the root of Stephania tetrandra S. Moore, the Chinese traditional medicine 'Fen-Fang-Ji', along with thirteen known alkaloids. The chemical structures of fenfangjines A, B, C, and D were determined to be tetrandrine 2-N-β-oxide, fangchinoline 2'-N-α-oxide, fangchinoline 2'-N- β-oxide, and 1,2,3,4-tetrahydrofangchinolinium hydroxide by spectral analyses and chemical methods, respectively.
Article
Two new secobisbenzylisoquinoline alkaloids, secocepharanthine (base J) (3) and O-methyl-punjabine (base K) (4), were isolated from Stephania sasakii Hayata (Menispermaceae). Their structures were established and the structures of two other alkaloids [base B (1) and base C (2)] were also established as dihydrosecocepharanthine (1) and O-methyldeoxopunjabine (2). In addition, two known bisbenzylisoquinoline alkaloids, obaberine (5) and thalrugosine (6), were newly isolated from the same plant. © 1985, The Pharmaceutical Society of Japan. All rights reserved.
Article
Twelve bisbenzylisoquinoline (BBI) alkaloids, tetrandrine, fangchinoline, tetrandrine 2'N-α-oxide, tetrandrine 2'-N-β-oxide, cycleahomine, 2'-N-methyltetrandrinium chloride, cycleanine, fenfangjine A, fenfangjine B, fenfangjine C, fenfangjine D, and 2,2'-N,N- dimethyltetrandrinium dichloride and two phenanthrene alkaloids, stephenanthrine and argentinine, and three benzylisoquinoline alkaloids, cyclanoline chloride, oblongine chloride, and magnoflorine chloride were isolated from a methanol extract of the root of Stephania tetrandra. In oder to clarify the structure activity relationship, 12 BBI alkaloids were tested for their inhibitory effects on angiotensin I converting enzyme. Of these isolated alkaloids, all the BBI alkaloids except cycleanine showed an inhibitory activity on angiotensin I converting enzyme.
Chapter
Publisher Summary This chapter presents information on hasubanan alkaloids. The chapter discusses the significant advances of the hasubanan group in discovering thirteen new congeners post-1970, including synthetic studies of the hasubanan skeleton. The occurrence of the hasubanan alkaloids has been noted in Stephania species only. The numbering system of the hasubanan skeleton (2,3,4,5- tetrahydro-3a,9b-butano-1 H - benz[e]indole) is used throughout this review. The chapter presents a table that presents a survey of the occurrence and physical constants of hasubanan alkaloids. The mass spectral feature exhibits a very characteristic fragmentation pattern and, therefore, provides a rapid and convenient method for structure elucidation of hasubanan alkaloids, especially, that of alkaloids obtained in small amounts. Alkaloids, such as hasubanonine, possessing a , β -unsaturated carbonyl group at C ring, show a similar breakdown pathway as that of metaphanine and others. Stephisoferuline was isolated from Stephania hernandifolia , and the presence of four methoxyl groups, one secondary amino group, a , β -unsaturated ester moiety, and two phenolic hydroxyl groups was shown. Hasubanonine and protostephanine have been shown by tracer experiments to be biosynthesized from two different C-6–C-2 units. Four 14 C-labeled amines and the putative isoquinoline intermediates were synthesized and tested in Stephania japonica plants.
Article
A new hasubanan ester-ketal alkaloid, named stephabenine, was isolated from the fresh fruits of Stephania japnica MIERS (Menispermaceae). Alkaline hydrolysis of the new base gave benzoic acid and a basic component, whose proton nuclear magnetic resonance spectrum was identical with that of authentic N, O-dimethylstephine.
Article
Four quaternary protoberberine alkaloids viz. palmatine (I), dehydrocorydalmine (II), palmatrubine (IV), stepharanine (V) and three tetrahydroprotoberberine alkaloids viz. tetrahydropalmatine (VI), corydalmine (VII) and stepholidine (VIII) have been isolated from the tubers of Stephania glabra. They have been characterised from their spectral (UV, IR, ¹H and ¹³C NMR and Mass) and chemical studies. ¹H-NMR of protoberberine salts (I-V) in D2O solutions are reported.
Article
The thermodynamic ionization constant K° of p-nitrophenol in {10 mass% ethanol-water} mixed solvent is derived from measurements of its absorption spectrum and pH by the two methods: Debye-Hückel extrapolation and polynomial approximation proposed by us in suitable buffer solution at constant ionic strength from 0.1 to 2.0 mol · kg−1 at 298.2 ± 0.2 K. The results from both methods are pK° = 7.406 and 7.415, respectively. The effect of medium on the ultraviolet spectra of p-nitrophenol has been discussed.
Article
Two new morphinane alkaloids named cephamonine (1) and cephamuline (2) were isolated from the tuber of Stephania cepharantha HAYATA (Menispermaceae), cultivated in Japan, along with eleven known alkaloids. By comparison of spectroscopic data with those of sinomenine (3), the structures of 1 and 2 were elucidated to be the 8-methoxy derivative of 3 and its C-14 stereoisomer, respectively.
Article
Spectroscopic methods and X-ray diffraction analysis have been used to elucidate the structure of the novel pentacyclic C-norhasubanan alkaloid stephadiamine isolated from Stephania japonica.
Article
Four new hasubanan alkaloids, stephamiersine (1), epistephamiersine (2), oxostephamiersine (3) and stephasunoline (4) were isolated together with seven known and three unidentified alkaloids from Stephania japonica MIERS (Menispermaceae). Among these new alkaloids, 1 and 2 were found to be epimeric isomers with respect to the C-7 methoxyl group. Permanganate oxidation of 1 gave 3, and borohydride reduction of 1 and 2 gave the highly stereoselective products, dihydrostephamiersine (6) and dihydroepistephamiersine (5). On mild treatment of 5 with hydrochloric acid gave 4. Acetolyses of 1, 2, 5 and 6 gave the phenanthrene derivatives, 7, 8 and 9, respectively. Further, both 1 and 2 were converted to the conjugated carbonyl compound (14) which was obtained from dihydro-16-oxohasubanonine (17a) (17b). On the other hand, the stereochemistry of 1, 2, 3 and 4 was elucidated by nuclear magnetic resonance (NMR) spectroscopic studies as follows : the C-7 methoxyl group of 1 has the α-axial and that of 2 and 4 has the β-equatorial configuration, and the hydroxyl group of 4 has the β-axial one. On the basis of the above chemical correlation coupled with the spectral arguments, the constitution of the new alkaloids was represented as drawn in the formulas, 1, 2, 3 and 4.
Article
The consitution of three new alkaloids, aknadinine (4-demethylhasubanonine) (4) from Stephania hermandifolia and S. Sasakii, aknadicine (4-demethylnorhasubanonine) (6) from S. hernandifolia, and aknadilactam (4-demehthyl-16-oxohasubanonine) (13) from S. Sasakii is discussed.
Article
A new aporphine alkaloid, kamaline, incorporating a novel urethane moiety and a glucoside unit, has been isolated from Stephania venosa.
Article
Investigation of the Chinese plant, Stephania sutchuenensis, has led to the isolation of aknadinine and a new natural analogue, 1-nitroaknadinine, whose structure was determined by spectroscopic analysis and chemical transformation.
Article
Although callus tissues derived from tubers of Stephania cepharantha cannot synthesize the main alkaloids of the original plant, cepharanthine and isotetrandrine, they are able to synthesize biscoclaurine alkaloids, berbamine and aromorine, the latter not being found in the original plant. These results suggest that enzymes controlling specific methylation and methylenedioxy group formation are absent from the callus. The maximum content of total alkaloid in the callus tissues subcultured for 9 months was more than 3 times that of original plant. Alkaloid content was affected by addition of various auxins, IAA being most effective.
Article
Six new protoberberines were found in Stephama suberosa root extracts: (−)-tetrahydrostephabine, (−)-stephabinamine, stephabine, 8-oxypseudopalmatine, (−)-trans-xylopinine N-oxide and (−)-cis-xylopinine N-oxide. Ten known alkaloids were also detected: (−)-tetrahydropalmatine, (−)-tetrahydropalmatrubine, (−)-stepholidine, (−)-kikemanine, (−)-capaurimine, (−)-coreximine, (−)-corytenchine, (−)-discretine, pseudopalmatine and (−)-xylopinine.
Article
Three hasubanane alkaloids, longetherine, stephabyssine and stephaboline were isolated from the aerial parts of Stephania longa. The structure of longetherine, a new hasubanane, was elucidated on the basis of spectroscopic analysis.
Article
A new hasubanan alkaloid named as runanine was isolated from Stephania sinica. On the basis of spectral analysis, four methoxyl groups could be located at C-2, C-3, C-7 and C-8, respectively. Its structure was determined to be 1. Two other known compounds, cepharanthine and sitosterol, were also obtained from this plant.
Article
Thirteen new hasubanan type alkaloids, stephalonines A-I (1-9), norprostephabyssine (15), isoprostephabyssine (16), isolonganone (18), and isostephaboline (21), as well as nine known ones, were isolated from the whole plants of Stephania longa, a well-known traditional Chinese medicine. Their structures were elucidated on the basis of spectroscopic data and chemical methods.
Article
Two new aporphine glycosides, stesakine-9-O-beta-D-glucopyranoside (1) and N-methylasimilobine-2-O-beta-D-glucopyranoside (2), were isolated from the seeds of Stephania cepharantha cultivated in Japan, together with 16 known alkaloids. The structures of 1 and 2 were spectroscopically determined by comparison of their H-1 and C-13 NMR data with those of stesakine (11) and N-methylasimilobine (12), respectively.
Article
Chromatographic separation of the EtOH extract from the aerial parts of Stephania tetrandra resulted in the isolation of a novel 4,5-dioxoaporphine alkaloid, stephadione {1}, together with six known alkaloids: corydione, oxonantenine, cassameridine, nantenine, cassythicine, and tetrandrine. The structure of stephadione was determined to be 6a,7-di-dehydro-1, 2;9,10-dimethylenedioxo-4,5-dioxo-N-methylaporphine by a consideration of spectral evidence.
Article
A new monoquaternary bisbenzylisoquinoline alkaloid, (+)-2-N-methylfangchinoline [4], was obtained from the root of Stephania tetrandra, the traditional Chinese medicine "fen-fang-ji," along with three known bisbenzylisoquinoline alkaloids 1-3.
Article
In a reinvestigation of the basic components of Stephania japonica, a new hasubanalactam alkaloid, named oxostephasunoline (1), was isolated from the roots. Its structure was established from consideration of spectral properties and by chemical conversion to 16-oxometaphanine (5) via 16-oxoprometaphanine (4). Oxostephasunoline (1), having a carbonyl group at C-16, is the sixth example of this type of compound isolated from natural sources.
Article
From the roots of Stephania cepharantha, a new morphinane alkaloid, named cephamorphinanine, was isolated along with seven known alkaloids including one aporphine, two morphinanes, one promorphinane and three bisbenzylisoquinolines. The structure of cephamorphinanine was established from spectral analysis and chemical correlation.