Rhizome Of Belamcanda Chinensis Research Articles

Cytotoxic Compounds from Belamcanda chinensis (L.) DC Induced Apoptosis in Triple-Negative Breast Cancer Cells.

Four compounds (1, 5, 7, and 8) were first isolated from the genus Belamcanda Adans. nom. conserv., and six known compounds (2-4, 6, 9, and 10) were isolated from the rhizome of Belamcanda chinensis (L.) DC. Their structures were confirmed by spectroscopic data. Herein, compounds 1-10 were rhapontigenin, trans-resveratrol, 5,7,4'-trihydroxy-6,3',5'-trimethoxy-isoflavone, irisflorentin, 6-hydroxybiochannin A, iridin S, pinoresinol, 31-norsysloartanol, isoiridogermanal, and iristectorene B, respectively. All compounds were evaluated for their antiproliferative effects against five tumor cell lines (BT549, 4T1, MCF7, MDA-MB-231, and MDA-MB-468). Among them, compound 9 (an iridal-type triterpenoid) showed the highest activity against 4T1 and MDA-MB-468 cells. Further studies displayed that compound 9 inhibited cell metastasis, induced cells cycle arrest in the G1 phase, exhibited significant mitochondrial damage in 4T1 and MDA-MB-468 cells including excess reactive oxygen species, decreased mitochondrial membrane potential, and induced 4T1 and MDA-MB-468 cell apoptosis for the first time. In summary, these findings demonstrate that compound 9 exerts promising potential for triple-negative breast cancer treatment and deserves further evaluation.

Soft rot disease of Belamcanda chinensis caused by Dickeya fangzhongdai in China

The rhizome of Belamcanda chinensis (belamcanda sinensis/Shegan) is an important traditional Chinese medicine, which is often used to treat lung diseases. However, soft rot disease seriously threatens the production of B. chinensis, causing its rhizomes to rot and the entire plant to die. Based on morphological characteristic and multigenic phylogenetic analyses of 16S rDNA, pel (pectate lyases encoding genes) and mdh (malic dehydrogenase encoding genes), the pathogenic isolates were identified as Dickeya fangzhongdai. One representative isolate SG-17 was selected for biological characteristics and pathogenicity tests analysis. The results showed that the optimum temperature and pH for SG-17 growth were 28 °C and pH 6, respectively. SG-17 caused typical soft rot symptoms on healthy B. chinensis plants, and produced symptoms of similar severity on Iris japonica (fringed iris) and Iris tectorum (iris), the other two species in Iridaceae family of economic and ornamental importance. Moreover, we also evaluated the impact of SG-17 on the contents of bioactive ingredients in B. chinensis rhizomes. The results show that the contents of tectorigenin and irigenin of B. chinensis rhizomes were increased significantly after infected with SG-17, while the contents of irisflorentin was decreased. As revealed by bactericides screen experiments, Ethylicin and Carbendazim · tetramethylthiuram disulfide exhibited good antibacterial activities, which could be used as the preferred agents for the control of soft rot of B. chinensis. As far as we know, this is the first report of Dickeya fangzhongdai causing soft rot on B. chinensis in the world.

New stilbenes and phenolic constituents from the rhizomes of Belamcanda chinensis

A pair of stilbenes with γ-lactam unit [(+)-1 and (−)-1], a new phenolic glucoside (2), and a new isoflavone glucoside (3), together with two known compounds (4-5) were isolated from the rhizomes of Belamcanda chinensis. The chemical structures of the undescribed compounds were elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 4, and 5 (10 μM) exhibited anti-inflammatory activities with inhibition rates of 30.46%, 60.34%, and 37.91%, respectively, against the NF-κB signaling pathway.

Isolation, Characterization and Anticomplementary Activity of Polysaccharides from the Rhizomes of Belamcanda chinensis (L.) DC.

The polysaccharides from the rhizomes of Belamcanda chinensis (L.) DC. (BCPs) were obtained by optimal water extraction (extraction temperature 84 °C, liquid to solid ratio 42 mL/g and extraction time 100 min), the extraction yield of BCPs was 23.01±0.27 % (n=3). Furthermore, two novel polysaccharides (BCP-A1 and BCP-B1) were purified by column chromatography. The BCP-A1 (6.0820×104 kDa) was composed of β-D-Manp-(1→, β-D-Glcp-(1→, →4)-α-D-Galp-(1→ and →3,4)-β-D-Galp-(1→, and BCP-B1 (2.2744×104 kDa) was composed of →5)-α-L-Araf-(1→, β-D-Manp-(1→, β-D-Glcp-(1→, →4)-α-D-Glcp, →4)-α-D-Galp-(1→, →4)-α-D-GalpA-(1→ and →3,4)-β-D-Galp-(1→. In anticomplementary experiments, BCP-A1 (CH50 : 0.009±0.003 mg/mL; AP50 : 0.015±0.003 mg/mL) and BCP-B1 (CH50 : 0.004±0.001 mg/mL; AP50 : 0.028±0.005 mg/mL) exhibited potent anticomplementary activity, and acted on C2-, C4- and Factor B components. Our study provides a foundation for BCP-A1 and BCP-B1 as potential complement inhibitors to treat diseases involving with excessive activation of the complement system.

Biological Activities and Therapeutic Potential of Irigenin on Gastric, Lung, Prostate, Breast, and Endometrial Cancer: Pharmacological and Analytical Aspects

Background: Herbal medicine has been in used in the medicine for thousands of years due to its multiple pharmacological activities against different types of human disorders. Biological effectiveness and pharmacological activities of herbal medicines is mainly due to the presence of different kinds of phytoconstituents commonly called secondary metabolites. Isoflavones are naturally present in different types of plants and food materials and most of these phytocompounds have a wide range of biological activities including anti-tumor, anti-proliferative, anti-inflammatory, anti-microbial, anti-viral, anti-oxidant, and estrogen-like activities. Methods: Irigenin isolated from the rhizome of Belamcanda chinensis and the genus Iris showed a wide range of biological activities. Due to huge biological potential and the therapeutic benefit of irigenin in the medicine, here in the present investigation, scientific research data of irigenin has been collected from different literature sources (Science Direct, Google Scholar, PubMed, Google) and analyzed in order to know the therapeutic potential of irigenin in the medicine. Pharmacological activities scientific data of irigenin have been collected from Science Direct, Google Scholar, PubMed, Google databases and analyzed in the present work. Importance of different analytical techniques for isolation and separation of irigenin has been also discussed and presented in the present work. Results: Scientific data analysis of different research work revealed the biological importance of irigenin in the medicine. Irigenin is an O-methylated isoflavone found to be present in the Belamcanda chinensis and genus Iris. Scientific data analysis revealed the biological importance of irigenin against gastric cancer, lung carcinoma, prostate cancer, breast cancer, endometrial cancer, diabetic complications, inflammation and cardiac injury. Analytical data of irigenin revealed the importance of analytical techniques for the separation, isolation and identification of irigenin from various biological samples. Conclusion: Scientific data analysis of different research works revealed the biological importance and therapeutic potential of irigenin in the medicine.

Tectoridin Stimulates the Activity of Human Dermal Papilla Cells and Promotes Hair Shaft Elongation in Mouse Vibrissae Hair Follicle Culture.

To search hair growth-promoting herbal extract, a screening platform of having HEK293T fibroblast being transfected with pTOPFLASH DNA construct was developed over a thousand of herbal extracts and phytochemicals were screened. One of the hits was ethanolic extract of Rhizoma Belamcandae, the rhizome of Belamcanda chinensis (L.) DC. Tectoridin, an isoflavone from Rhizoma Belamcandae, was shown to be responsible for this activation of promoter construct, inducing the transcription of pTOPFLASH in the transfected fibroblasts in a dose-dependent manner. The blockage by DKK-1 suggested the action of tectoridin could be mediated by the Wnt receptor. The hair growth-promoting effects of tectoridin were illustrated in human follicular dermal papilla cells and mouse vibrissae organ cultures. In tectoridin-treated dermal papilla cultures, an activation of Wnt signaling was demonstrated by various indicative markers, including TCF/LEF1 transcriptional activity, nuclear translocation of β-catenin, expressions level of mRNAs encoding axin-related protein, (AXIN2), β-catenin, lymphoid enhancer-binding factor-1 (LEF-1), insulin-like growth factor 1 (IGF-1) and alkaline phosphatase (ALP). In addition, an increase of hair shaft elongation was observed in cultured mouse vibrissae upon the treatment of tectoridin. Tectoridin, as well as the herbal extract of Rhizoma Belamcandae, possesses hair promoting activity, which deserves further development.

New iridal-type triterpenoid analogues with 6/5/6-fused carbon skeleton from the rhizomes of Belamcanda chinensis

Five new iridal-type triterpenoid derivatives with 6/5/6 tricyclic ring skeleton (1–5) were obtained from the rhizomes of Belamcanda chinensis. Their structures were determined on the basis of detailed spectroscopic data and ECD calculation. Compounds 1–5 possessed the same 6/5/6-fused carbon skeleton as Belamchinenin A, which further enriched this kind of iridals. In vitro bioassay, compounds 2 and 3 exhibited 51.95 and 54.52% inhibitory activities, respectively, against Fe2+/cysteine-induced liver microsomal lipid peroxidation at a concentration of 10 μM. A putative biogenetic pathway for compounds 1–5 was proposed.

Irigenin reduces the expression of caspase-3 and matrix metalloproteinases, thus suppressing apoptosis and extracellular matrix degradation in TNF-α-stimulated nucleus pulposus cells

Irigenin, an isoflavonoid isolated from the rhizome of Belamcanda chinensis, possess various pharmacological effects. However, the effect and mechanism of irigenin on intervertebral disc degeneration (IDD) remain unclear. The potential targets of irigenin or disease were predicted using PharmMapper or GeneCards databases, respectively. The overlapping targets were inputted into the String database to establish protein-protein interaction (PPI) network. The overlapping targets were also submitted to DAVID webserver to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Nucleus pulposus (NP) cells were exposed to 10 ng/mL tumor necrosis factor-α (TNF-α) to establish a cell model of IDD. Cell viability, LDH content, apoptosis and caspase-3 activity were evaluated by CCK-8, LDH release, TUNEL, and caspase-3 activity assays, respectively. The expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 were detected by qRT-PCR and western blot analyses. The network analysis revealed that MMP-2, MMP-3, MMP-9, MMP-13, caspase-3 (CASP3), vitamin D receptor (VDR), insulin-like growth factor 1 (IGF1), and transforming growth factor beta2 (TGFB2) play key roles in the effect of irigenin against IDD. TNF-α stimulation inhibited cell viability and increased LDH content, apoptosis, caspase-3 expression and caspase-3 activity in NP cells, which were reversed by irigenin treatment. TNF-α stimulation inhibited the expression of collagen II and aggrecan and upregulated MMPs (MMP-2, MMP-3, MMP-9, and MMP-13) in NP cells, while such changes were abolished by irigenin treatment. In conclusion, irigenin suppressed apoptosis and ECM degradation in TNF-α-stimulated NP cells by reducing the expression of caspase-3 and MMPs.

Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425

Doxorubicin (DOX) is an eff ;ective chemotherapeutic drug to suppress the progression of various types of tumors. However, its clinical application has been largely limited due to its potential cardiotoxicity. MicroRNAs (miRNAs) are emerged as critical regulators of cardiac injury. This study was aimed to explore the effects of irigenin (IR), as an isoflavonoid isolated from the rhizome of Belamcanda chinensis, on DOX-induced cardiotoxicity using the in vivo and in vitrostudies. The results indicated that DOX-induced fibrosis, cardiac dysfunction and injury were markedly attenuated by IR through reducing apoptosis, oxidative stress and inflammation in heart tissue samples. Importantly, DOX resulted in a remarkable decrease of miR-425 in heart tissues and cells, which was significantly rescued by IR. Receptor-interacting protein kinase 1 (RIPK1) was discovered to be a direct target of miR-425. DOX induced over-expression of RIPK1 both in vivo and in vitro, which were greatly decreased by IR. Transfection with miR-425 mimic could inhibit RIPK1 expression, whereas reducing miR-425 increased RIPK1 expression levels. In parallel to miR-425 over-expression, RIPK1 knockdown could attenuate apoptosis, reactive oxygen species (ROS) production and inflammation in HL-1 cells. However, over-expression of RIPK1 markedly abolished miR-425 mimic-induced apoptosis, ROS accumulation and inflammatory response in DOX-exposed cells. Herein, miR-425 could ameliorate cardiomyocyte injury through directly targeting RIPK1. Furthermore, activation of miR-425 by IR markedly improved DOX-induced cardiotoxicity, and therefore IR could be considered as a promising therapeutic agent for the treatment of cardiac injury.

Tectorigenin, an isoflavone aglycone from the rhizome of Belamcanda chinensis, induces neuronal expression of erythropoietin via accumulation of hypoxia-inducible factor-1α.

Traditional Chinese medicines (TCMs) have been demonstrated as an important source for potential drug discovery. Flavonoids are regarded as the most common active components in TCMs because of their beneficial functions in the brain and erythropoietic system. Erythropoietin (EPO), a glycoprotein hormone, has been well-studied for its neuroprotective function. The blood circulating EPO is not able to cross the blood brain barrier, and thus there is mounting demand to search for compounds that can induce endogenous cerebral EPO. Here, tectorigenin, an active compound in the rhizome of Belamcanda chinensis (L.) DC., significantly induced the expression of EPO mRNA via accumulation of hypoxia-inducible factor (HIF)-1α in cultured neuron-like NT2/D1 cells and rat cortical neurons. Furthermore, tectorigenin induced transcription of HIF-1α and reduced degradation of HIF-1α-OH, a hydroxylated form of HIF-1α, in the culture. Thus, the upregulation of HIF-1α was assumed to play a significant role in regulating EPO during the treatment of tectorigenin in cultured neurons. Hence, we reported the neuroprotective function of tectorigenin through upregulation of EPO in neurons, which could be a good candidate in developing drugs or food supplements for the treatment of brain disorders.

Iridal-Type Triterpenoids with a Cyclopentane Unit from the Rhizomes of Belamcanda chinensis.

Ten new iridal-type triterpenoid derivatives, polycycloiridals K-T (1-10), with a cyclopentane moiety originating from the cyclization of the homofarnesyl side chain were isolated from the rhizomes of Belamcanda chinensis. Their structures were established by spectroscopic data, a single-crystal X-ray diffraction analysis, TDDFT quantum mechanical calculations, and chemical derivatization. Compounds 2 and 10 exhibited 33.4% and 32.9% inhibitory activities, respectively, against PTP1b (protein tyrosine phosphatase) at a concentration of 10 μM. A putative biosynthetic pathway is proposed.

Seconoriridone A: A C16-seco-noriridal derivative with a 5/5/7 tricyclic skeleton from Belamcanda chinensis

Seconoriridone A (1), a novel C16-seco-noriridal with a 5/5/7 tricyclic scaffold, was isolated from the rhizome of Belamcanda chinensis. Its structure and absolute configuration were determined by NMR spectroscopy and quantum chemical calculations. Notably, seconoriridone A featured a 2-butanonyl moiety with oxidative cleavage of the conventionally multisubstituted cyclohexane ring of iridals. Seconoriridone A was a mixture of C-14 epimers in the presence of hemiacetal. The plausible biosynthetic pathway for 1 was deduced.

New iridal-type triterpenoid derivatives with cytotoxic activities from Belamcanda chinensis

Eight new iridal-type triterpenoid derivatives, including two noriridals with ether bridge (1–2); two iridals lactone (3–4), four monocyclic iridals (5–8), together with five known iridals (9–14) were identified from the rhizome of Belamcanda chinensis. Their structures were elucidated on the basis of comprehensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Bioassay results showed that belamcanoxide B (1) exhibited moderated cytotoxic activities against HCT-116 and MCF-7 cell lines with IC50 values of 5.58 and 3.35 μM.

Tectorigenin Promotes Osteoblast Differentiation and in vivo Bone Healing, but Suppresses Osteoclast Differentiation and in vivo Bone Resorption.

Although tectorigenin (TG), a major compound in the rhizome of Belamcanda chinensis, is conventionally used for the treatment of inflammatory diseases, its effects on osteogenesis and osteoclastogenesis have not been reported. The objective of this study was to investigate the effects and possible underlying mechanism of TG on in vitro osteoblastic differentiation and in vivo bone formation, as well as in vitro osteoclast differentiation and in vivo bone resorption. TG promoted the osteogenic differentiation of primary osteoblasts and periodontal ligament cells. Moreover, TG upregulated the expression of the BMP2, BMP4, and Smad-4 genes, and enhanced the expression of Runx2 and Osterix. In vivo studies involving mouse calvarial bone defects with μCT and histologic analysis revealed that TG significantly increased new bone formation. Furthermore, TG treatment inhibited osteoclast differentiation and the mRNA levels of osteoclast markers. In vivo studies of mice demonstrated that TG caused the marked attenuation of bone resorption. These results collectively demonstrated that TG stimulated osteogenic differentiation in vitro, increased in vivo bone regeneration, inhibited osteoclast differentiation in vitro, and suppressed inflammatory bone loss in vivo. These novel findings suggest that TG may be useful for bone regeneration and treatment of bone diseases.

Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment.

Belamcandanes A and B, two unprecedented tricyclic-iridal triterpenoids from Belamcanda chinensis

Two unprecedented tricyclic-iridal triterpenoids, belamcandanes A–B (1–2), have been isolated from the rhizomes of Belamcanda chinensis. The structures of 1 and 2 were assigned by interpretation of spectroscopic data including NMR and MS, and their absolute configurations were assigned by ECD calculation. Compounds 1–2 possess a spiro[4,5]decane core structure and a α-terpineol moiety, representing the first example of tricyclic-iridal triterpenoids. The plausible biogenetic pathway for 1 and 2 is also proposed.

The unprecedented iridal lactone and adducts of spiroiridal and isoflavonoid from Belamcanda chinensis

Five novel iridal-type triterpenoid derivatives have been isolated from the rhizomes of Belamcanda chinensis, along with five known compounds. Their structures were elucidated by extensive spectroscopic analysis.

Anti-inflammatory Effect of (7R,8S)-dehydrodiconiferyl Alcohol-92 A-methyl Ether from the Rhizome of Belamcanda Chinensis: Role of miR-146a and miR-155

Anti-inflammatory Effect of (7R,8S)-dehydrodiconiferyl Alcohol-92 A-methyl Ether from the Rhizome of Belamcanda Chinensis: Role of miR-146a and miR-155

<i>Belamcanda chinensis</i> (l.) Dc: Ethnopharmacology, phytochemistryand pharmacology of an important traditional Chinese medicine

Background: Belamcanda chinensis (L.) DC (Iridaceae), a widely used traditional Chinese medicine known as She Gan (Chinese: 射干), is a flowering perennial herb native to East Asia. For thousands of years in China, the rhizome of Belamcanda chinensis has been used to treat inflammation, oxyhepatitis, mumps, acute mastitis, and asthma, as well as throat disorders such as cough, tonsillitis and pharyngitis. Belamcanda chinensis is now listed in the Pharmacopoeia of the People’s Republic of China. The present paper reviews the advancements in the investigation of botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Belamcanda chinensis . Materials and Methods: Information on Belamcanda chinensis was collected from scientific journals, books, theses and reports via library and electronic search (PubMed, CNKI, Elsevier, ACS, Google Scholar, Baidu Scholar,Web of Science and Science Direct). Results: A number of chemical compounds have been isolated from Belamcanda chinensis , and the major isolated compounds have been identified as isoflavonoids, flavonoids and iridal-type triterpenoids. Among these active compounds, the effects of tectoridin and tectorigenin have been widely investigated. The primary active components in Belamcanda chinensis possess a wide range of pharmacological activities, including anti-inflammatory, anti-oxidative, anti-tumour, anti-alcohol injury, cardiovascular and oestrogenic activities. Conclusions: As an important traditional Chinese medicine, Belamcanda chinensis has been demonstrated to have marked bioactivity, especially in the respiratory system and as an oestrogenic and hepatoprotective agent. This activity is related to its traditional use and provides opportunities for the development of novel drugs and therapeutic products for various diseases. However, the toxicity of Belamcanda chinensis will require further study, and more attention should be devoted to its better utilization. Keywords: Belamcanda chinensis ; Ethnopharmacology; Phytochemistry; Pharmacology; Toxicology

BELAMCANDA CHINENSIS (L.) DC: ETHNOPHARMACOLOGY, PHYTOCHEMISTRY AND PHARMACOLOGY OF AN IMPORTANT TRADITIONAL CHINESE MEDICINE

Background: Belamcanda chinensis (L.) DC (Iridaceae), a widely used traditional Chinese medicine known as She Gan (Chinese: 射干), is a
 flowering perennial herb native to East Asia. For thousands of years in China, the rhizome of Belamcanda chinensis has been used to treat
 inflammation, oxyhepatitis, mumps, acute mastitis, and asthma, as well as throat disorders such as cough, tonsillitis and pharyngitis. Belamcanda
 chinensis is now listed in the Pharmacopoeia of the People’s Republic of China. The present paper reviews the advancements in the investigation
 of botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Belamcanda chinensis.
 Materials and Methods: Information on Belamcanda chinensis was collected from scientific journals, books, theses and reports via library and
 electronic search (PubMed, CNKI, Elsevier, ACS, Google Scholar, Baidu Scholar,Web of Science and Science Direct).
 Results: A number of chemical compounds have been isolated from Belamcanda chinensis, and the major isolated compounds have been
 identified as isoflavonoids, flavonoids and iridal-type triterpenoids. Among these active compounds, the effects of tectoridin and tectorigenin
 have been widely investigated. The primary active components in Belamcanda chinensis possess a wide range of pharmacological activities,
 including anti-inflammatory, anti-oxidative, anti-tumour, anti-alcohol injury, cardiovascular and oestrogenic activities.
 Conclusions: As an important traditional Chinese medicine, Belamcanda chinensis has been demonstrated to have marked bioactivity, especially
 in the respiratory system and as an oestrogenic and hepatoprotective agent. This activity is related to its traditional use and provides
 opportunities for the development of novel drugs and therapeutic products for various diseases. However, the toxicity of Belamcanda chinensis
 will require further study, and more attention should be devoted to its better utilization.