Rhizomes Of Astilbe Chinensis Research Articles

3β-Hydroxy-12-oleanen-27-oic Acid Exerts an Antiproliferative Effect on Human Colon Carcinoma HCT116 Cells via Targeting FDFT1.

3β-hydroxy-12-oleanen-27-oic acid (ATA), a cytotoxic oleanane triterpenoid with C14-COOH isolated from the rhizome of Astilbe chinensis, has been previously proven to possess antitumor activity and may be a promising antitumor agent. However, its molecular mechanisms of antitumor action were still unclear. This study explored the underlying mechanisms of cytotoxicity and potential target of ATA against human colorectal cancer HCT116 cells via integrative analysis of transcriptomics and network pharmacology in combination with in vitro and in vivo experimental validations. ATA significantly inhibited the proliferation of HCT116 cells in a concentration- and time-dependent manner and induced the cell cycle arrest at the G0/G1 phase, apoptosis, autophagy, and ferroptosis. Transcriptomic analysis manifested that ATA regulated mRNA expression of the genes related to cell proliferation, cell cycle, and cell death in HCT116 cells. The integrated analysis of transcriptomics, network pharmacology, and molecular docking revealed that ATA exerted cytotoxic activity via interactions with FDFT1, PPARA, and PPARG. Furthermore, FDFT1 was verified to be an upstream key target mediating the antiproliferative effect of ATA against HCT116 cells. Of note, ATA remarkably suppressed the growth of HCT116 xenografts in nude mice and displayed an apparent attenuation of FDFT1 in tumor tissues accompanied by the alteration of the biomarkers of autophagy, cell cycle, apoptosis, and ferroptosis. These results demonstrate that ATA exerted in vitro and in vivo antiproliferative effects against HCT116 cells through inducing cell apoptosis, autophagy, and ferroptosis via targeting FDFT1.

Ultrasound-assisted extraction of bergenin from Astilbe chinensis

Bergenin is the main and effect compound in root and rhizome of Astilbe chinensis (Maxim.) Franch. et Savat., which possesses antiarthritis, anti-HIV, antiarrhythmic, antihepatotoxicity and antiulcer properties. In this study, the ultrasound-assisted extraction (UAE) condition of bergenin from A. chinensis was investigated with HPLC-photodiode array detection, in which the effects of several affecting parameters were evaluated, such as electrical acoustic intensity, solvent type, biomass to solvent ratio, extraction temperature and time. The optimal extraction condition was 45 % ethanol, biomass to solvent ratio 1:20, and extraction for 20 min at 50 °C under 50 W acoustic intensity. Under this optimal condition, the bergenin yield was 61.90 mg/g sample, significantly higher than that by heat reflux method in this species and some methods in other species. The results indicated that the UAE is a convenient and rapid method for harvesting higher yield of bergenin from A. chinensis.

A new triterpene from Astilbe chinensis

A new triterpene, 3β,19α-dihydroxy-6β-acetoxy-ursane (1), was isolated from the rhizomes of Astilbe chinensis. Its structure was elucidated on the basis of 1D and 2D NMR analyses and HR-MS experiments. The isolated compound exhibited cytotoxic activities against HeLa and L929 cell lines.

The Inhibitory Effect of 3 β -Hydroxy-12-oleanen-27-oic Acid on Growth and Motility of Human Hepatoma HepG2 Cells through JNK and Akt Signaling Pathway.

3β-Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes of Astilbe chinensis. In this study, we investigated its effects on growth, apoptosis, cell cycle, motility/invasion, and metatasis in human hepatoma HepG2 cells in vitro and antimetastasis of B16-F10 melanoma in mice in vivo, as well as its molecular mechanisms of action using a high-throughput Cancer Pathway Finder PCR Array. ATA could not only induce tumor cells into apoptosis through the activation of both extrinsic and intrinsic pathways, arrest HepG2 cells in G2/M phase, but also suppress the invasion and metastasis abilities of HepG2 cells and the lung metastasis of B16-F10 melanoma in mice. PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4. These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

Chemical constituents from Astilbe chinensis

A new compound, 11-O-(3′-O-methylgalloyl)-bergenin (1), along with 11 known compounds (2–12), has been isolated from the rhizome of Astilbe chinensis. The chemical structure of compound 1 was determined by IR, MS, and NMR spectral data. All compounds were evaluated for the cytotoxic activity in vitro, and compound 4 showed a moderate cytotoxic activity against HepG2 cells.

Immunomodulatory Activity of 3β,6β‐Dihydroxyolean‐12‐en‐27‐oic Acid in Tumor‐Bearing Mice

3beta,6beta-dihydroxyolean-12-en-27-oic acid (1) is a pentacyclic triterpenoid isolated from the rhizomes of Astilbe chinensis. To evaluate the in vivo antitumor potential and to elucidate its immunological mechanisms, effect of 1 on the growth of mouse-transplantable tumors, and the immune response in naive and tumor-bearing mice were investigated. The mice inoculated with mouse tumor cell lines were orally treated with 1 at the doses of 40, 60, and 80 mg/kg for 10 days. The effects of 1 on the growth of mouse-transplantable S180 sarcoma and H22 hepatoma, splenocyte proliferation, cytotoxic T lymphocyte (CTL) activity, natural killer (NK) cell activity, and production of interleukin-2 (IL-2) from splenocytes in S180-bearing mice were measured. Furthermore, the effect of 1 on 2,4-dinitrofluorobenzene (DNFB)-induced delayed-type hypersensitivity (DTH) reactions and the sheep red blood cell (SRBC)-induced antibody response in naive mice were also studied. Compound 1 could not only significantly inhibit the growth of mouse transplantable S180 sarcoma and H22 hepatoma, increase splenocytes proliferation, CTL and NK cell activity, and the level of IL-2 secreted by splenocytes in tumor-bearing mice, but also remarkably promote the DTH reaction and enhance anti-SRBC antibody titers in naive mice. These results suggested that 1 could improve both cellular and humoral immune response, and could act as antitumor agent with immunomodulatory activity.

Potent Antielastase and Antityrosinase Activities of Astilbe chinensis

Problem statement: In the current scenario, photo-aging is a major problem causing skin wrinkling and hyperpigmentation. Therefore, elastase and tyrosinase inhibitors play an important role in the treatment of skin aging and thus, gaining a special attention in cosmetic industries. Approach: In the screening of Korean medicinal plants to search the potent elastase and tyrosinase inhibitors, the extract of the rhizomes of Astilbe chinensis (A. chinensis) exhibited the strongest potential. Further the crude 100% methanolic extract of A. chinensis along with its n-hexane, methylene chloride, ethyl acetate and aqueous fractions were investigated for elastase and tyrosinase enzyme inhibition activities. Results: The A. chinensis extracts showed remarkable elastase inhibitory activities (at a concentration of 20 μg 155 μL-1 reaction) ranging from 38-92% and tyrosinase inhibition activities (at a concentration of 20 μg 150 μL-1 reaction) ranging from 2-90%. Among all the fractions, water fraction demonstrated the highest elastase and tyrosinase inhibitory activities (92 and 90%, respectively). Conclusion: Based on the noteworthy antielastase and antityrosinase activities by the rhizome of A. chinensis, it might prove a strong candidate as an active ingredient in cosmaceutical formulations and further in vitro and in vivo investigations is needed.

Triterpenes from Astilbe chinensis

Six new triterpenes, 3β,6β-dihydroxyurs-12-en-27-oic acid (1), 3β,6β,24-trihydroxyurs-12-en-27-oic acid (2), 3β,6β,7α-trihydroxyurs-12-en-27-oic acid (3), 3β-acetoxy-6β-hydroxyurs-12-en-27-oic acid (4), 3β,6β,24-trihydroxyolean-12-en-27-oic acid (5), and 3β,6β,7α-trihydroxyolean-12-en-27-oic acid (6), were isolated from the rhizomes of Astilbe chinensis. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses and HR-MS experiments. The isolated compounds exhibited significant cytotoxic activities against the SK-N-SH and HL-60 cell lines.

Astilbotriterpenic Acid Induces Growth Arrest and Apoptosis in HeLa Cells through Mitochondria‐Related Pathways and Reactive Oxygen Species (ROS) Production

Astilbotriterpenic acid, a novel ursane-type triterpenoid from the rhizomes of Astilbe chinensis, has cytostatic properties in several cancer cell lines and induces apoptosis in HeLa cell. The aim of this study was to investigate the mechanisms by which such properties are exerted, with special reference to the anti-proliferative and apoptotic potential on HeLa cells. Compound 1 showed a marked concentration- and time-dependent inhibition of HeLa cell proliferation, and induced G(0)/G(1) phase arrest of HeLa cell in a dose-dependent manner. There was a quick attenuation of mitochondrial membrane potential (Deltapsi(m)) with the alterations of Bcl-2/Bax mRNA express value in 1-treated HeLa, indicating the participation of a mitochondria-related mechanism. Pretreatment of a pan-caspase inhibitor (benzyloxycarbonyl)-Val-Ala-Asp-(fluoromethyl) ketone (z-VAD-fmk) significantly increases the viability of 1-treated HeLa cells implied that the participation of caspase; Western-blot analysis showed the activation of initiator caspase-8 and caspase-9, and executor caspase-3. Meanwhile, treatment with 1 stimulates the generation of reactive oxygen species (ROS) in HeLa cell. Taken together, our data showed that compound 1 induced growth arrest and apoptosis in HeLa cells through mitochondria-related pathways and ROS production, and may be further evaluated as a chemotherapeutic agent for human cancer.

132 POSTER SRJ09, a lead compound in anticancer drug design: in vitro, in vivo and mechanistic studies

The objectives of this study were to investigate the protective effect of the triterpenoid fractions from the rhizomes of Astilbe chinensis (Saxifragaceae) (ATF) on cyclophosphamide (CTX)-induced toxicity in tumor-bearing mice.The mice inoculated with mouse sarcoma S180 cells were treated with saline or CTX alone, or co-treated with CTX and ATF. The blood, femur bone, and serum samples were collected for determination of the haematological and biochemical parameters and splenocytes were for assay of proliferation, the activity of natural killer (NK) cells, and production of interleukin-2 (IL-2).ATF significantly increased the peripheral white blood cell (WBC) count and bone marrow cellularity (BMC) in CTX-treated S180-bearing mice. Increase of aspartate transanimase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine in the serum of CTX-treated mice was significantly reversed by ATF. The lowered levels of splenocytes proliferation, NK cells activity, and IL-2 production from splenocytes in S180-bearing mice after CTX treatment were also increased by ATF administration.ATF provides significant protection against CTX-induced hematotoxicity, hepatotoxicity, nephrotoxicity, and immunotoxicity, and might be helpful in abrogation of CTX-induced toxicity during the chemotherapy.

Protective effect of triterpenoid fractions from the rhizomes of Astilbe chinensis on cyclophosphamide-induced toxicity in tumor-bearing mice

Aim of the study The objectives of this study were to investigate the protective effect of the triterpenoid fractions from the rhizomes of Astilbe chinensis (Saxifragaceae) (ATF) on cyclophosphamide (CTX)-induced toxicity in tumor-bearing mice. Materials and methods The mice inoculated with mouse sarcoma S180 cells were treated with saline or CTX alone, or co-treated with CTX and ATF. The blood, femur bone, and serum samples were collected for determination of the haematological and biochemical parameters and splenocytes were for assay of proliferation, the activity of natural killer (NK) cells, and production of interleukin-2 (IL-2). Results ATF significantly increased the peripheral white blood cell (WBC) count and bone marrow cellularity (BMC) in CTX-treated S180-bearing mice. Increase of aspartate transanimase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine in the serum of CTX-treated mice was significantly reversed by ATF. The lowered levels of splenocytes proliferation, NK cells activity, and IL-2 production from splenocytes in S180-bearing mice after CTX treatment were also increased by ATF administration. Conclusions ATF provides significant protection against CTX-induced hematotoxicity, hepatotoxicity, nephrotoxicity, and immunotoxicity, and might be helpful in abrogation of CTX-induced toxicity during the chemotherapy.

Immunomodulatory and antitumor activity of triterpenoid fractions from the rhizomes of Astilbe chinensis

Aim of the study The objectives of this study were to evaluate the in vivo antitumor potential of the triterpenoid fraction from the rhizomes of Astilbe chinensis (Saxifragaceae) (Saxifragaceae) (ATF) and to elucidate its immunological mechanisms by determining its effects on the growth of mouse transplanted tumors and the immune response in naïve and tumor-bearing mice. Materials and methods The mice inoculated with mouse tumor cell lines were treated per os with ATF at the doses of 20, 40, 60 mg/kg for 10 days. The effects of ATF on the growth of transplantable tumor, splenocyte proliferation, the activity of natural killer (NK) cells, and production of interleukin-2 (IL-2) from splenocytes in tumor-bearing mice were measured. Meanwhile, the effects of ATF on 2,4-dinitrofluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) reaction and the sheep red blood cell (SRBC)-induced antibody response in naïve mice were also studied. Results ATF could not only significantly inhibit the growth of mice transplantable tumor, but also remarkably increase splenocytes proliferation, NK cells activity, and the level of IL-2 secreted by splenocytes in tumor-bearing mice, promote the DTH reaction and enhance anti-SRBC antibody level in naïve mice, which indicated that the ATF could improve both specific and non-specific cellular and humoral immune response. Conclusions The antitumor activity of ATF might be achieved by improving immune response, and ATF could act as antitumor agent with immunomodulatory activity.

A New Cytotoxic, Apoptosis‐Inducing Triterpenoid from the Rhizomes of Astilbe chinensis

A new ursane-based compound, astilbotriterpenic acid (1), was isolated from the rhizomes of Astilbe chinensis. Its structure was determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D- and 2D-NMR. The pentacyclic triterpenoid 1 was assayed for its in vitro cytotoxicity against Bcap37, HeLa, HepG2, HO-8910, K562, PAA, SGC7901, and P388 cancer cells, as well as for its apoptosis-inducing activity in HeLa cells. Compound 1 was found to strongly inhibit tumor-cell growth through induction of apoptosis and may, thus, be further evaluated as a novel chemotherapeutic agent.

2β,24-Dihydroxyurs-12-en-27-oic acid methanol solvate from the rhizome ofAstilbe chinensis

The title compound, a novel triterpenoid, C30H48O4·CH4O, was isolated from the rhizome of Astilbe chinensis (Maxim.) Franch. et Sav. It contains five fused six-membered rings, which adopt half-chair conformations. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules, forming an extensive network, which may be effective in the stabilization of the structure.

Induction of Apoptosis in HeLa Cells by 3β‐Hydroxyurs‐12‐en‐27‐oic Acid

3Beta-hydroxyurs-12-en-27-oic acid (1), a pentacyclic triterpenoid isolated from the rhizomes of Astilbe chinensis, was structurally very similar to ursolic acid, with the only difference being the interchange of the COOH and Me group at C(14) and C(17). Ursane-type triterpene with a COOH group at C(14) is present in a limited number of natural resources. Compound 1 was found to exhibit more distinctive cytotoxicity toward human cervical squamous carcinoma (HeLa) cells than ursolic acid, suggesting that the position of the COOH group significantly affects the cytotoxicity of ursane-type pentacyclic triterpenes with a COOH group. To elucidate the underlying biological mechanism responsible for the cytotoxicity of 1, we investigated its growth-inhibitory and apoptosis-inducing effect on HeLa cells. Compound 1 induced a marked concentration- and time-dependent inhibition of cell proliferation with an IC50 value of 6.80+/-0.88 microg/ml following 48 h incubation. The drug-treated HeLa cells displayed typical morphological apoptotic characteristics and formation of DNA ladders in agarose-gel electrophoresis. Flow cytometric analysis showed that the cell cycle was arrested in G0/G1 phase by 1, and the apoptotic rate of HeLa cells treated for 48 h with 20 microg/ml of 1 was 21.08+/-2.14%. Also, 1 increased and decreased the expression of Bax and Bcl-2 proteins, respectively, and lowered the mitochondrial transmembrane potential (delta psi(m)). The peptidic caspase-3 inhibitor DEVD-CHO (NH2-Asp-Glu-Val-Asp-CHO, at 2 microM) could increase the viability of HeLa cells previously treated with 1. These results indicate that 1 induces efficient cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering delta psi(m), and by activating the caspase-3 pathway.

3β‐Hydroxyolean‐12‐en‐27‐oic Acid: A Cytotoxic, Apoptosis‐Inducing Natural Drug Against COLO‐205 Cancer Cells.

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3β-Hydroxyolean-12-en-27-oic Acid: A Cytotoxic, Apoptosis-Inducing Natural Drug against COLO-205 Cancer Cells

3Beta-hydroxyolean-12-en-27-oic acid (1), a biologically active, pentacyclic triterpenoid isolated from the rhizomes of Astilbe chinensis, was found to be considerably more cytotoxic toward human colorectal carcinoma (COLO-205) and human cervical squamous carcinoma (HeLa) cells than its congener oleanolic acid (4). This suggests that the position of the COOH group significantly affects the cytotoxicity of oleanane-type pentacyclic triterpene carboxylic acids. To elucidate the underlying biological mechanism responsible for the cytotoxicity of 1, we investigated its growth-inhibitory effect on COLO-205 cells. Compound 1 induced a marked concentration- and time-dependent inhibition of cell proliferation, with the typical morphological characteristics of apoptosis, and under formation of DNA ladders in agarose-gel electrophoresis. Flow-cytometric analysis showed that the cell cycle of COLO-205 cells exposed to 1 was arrested in the G0/G1 phase. Also, 1 increased and decreased the expression of Bax and Bcl-2 proteins, respectively, and lowered the mitochondrial transmembrane potential (delta psi(m)). The peptidic caspase-3 inhibitor NH2-Asp-Glu-Val-Asp-CHO (at 1 microM) could increase the viability of COLO-205 cells previously treated with 1. These results indicate that 1 induces efficient cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering delta psi(m), and by activating the caspase-3 pathway.

Induction of apoptosis in HeLa cells by 3β-hydroxy-12-oleanen-27-oic acid from the rhizomes of Astilbe chinensis

3β-Hydroxy-12-oleanen-27-oic acid (ATA) was an antitumor active oleanane-type triterpenoid from the rhizomes of Astilbe chinensis. ATA was structurally very similar to oleanolic acid, with the only difference being interchange of the carboxyl and methyl group at the C-14 and C-17 positions. Oleanane-type triterpene with a carboxyl group at C-14 is present in a limited number of natural resources. ATA was found to exhibit more distinctive cytotoxicity toward human cervical squamous carcinoma HeLa cells than oleanolic acid, which suggested that the position of the carboxyl group significantly affects the cytotoxicity of oleanane-type pentacyclic triterpenes with a carboxyl group. The biological mechanism responsible for the cytotoxicity of ATA is not yet well understood. In this study, we investigated the induction of apoptosis in HeLa cells by ATA and the putative pathways of its actions. ATA induced a marked concentration- and time-dependent inhibition of HeLa cell proliferation, and reduced the protein content in HeLa cells. ATA-treated HeLa displayed typical morphological apoptotic characteristics and formation of DNA ladders in agarose gel electrophoresis. Flow cytometric analysis showed that the HeLa cell cycle was arrested in the G 0/ G 1 phase by ATA, and the apoptotic rate of HeLa cells treated with ATA 20 μg/mL for 48 h was 22.63 ± 1.65%. Meanwhile, ATA increased the expression of Bax, decreased the expression of Bcl-2, and lowered the Δ Ψ m. DEVD-CHO 2 μM could increase the viability of ATA-treated HeLa cells. These results indicate that ATA could significantly induce cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering Δ Ψ m, and activating the caspase-3 pathway, and should be useful in the search for new potential anti-tumor agents and for developing semisynthetic oleanane-type triterpene derivatives with anti-tumor activity.

Effect of the rhizomes ofAstilbe chinensison UVB‐induced inflammatory response

The EtOH extract from the rhizomes of Astilbe chinensis (Saxifragaceae) exhibited potent antioxidant activity in preliminary screening. Since oxidative stress is known to be involved in the inflammatory response after UVB exposure, the ability of an A. chinensis extract to inhibit UVB-induced PGE2 and NO production was examined. UVB irradiation (35 mJ/cm2) increased PGE2 and NO production, which were significantly decreased by pre-administration of the extract in a dose-dependent manner. The A. chinensis extract also preserved the cellular antioxidant capacity after UVB irradiation, which was determined by the GSH content. UVB irradiation enhanced the formation of ROS in the keratinocytes, which was determined using DCFH-DA, a redox sensitive dye. The levels of intracellular ROS were also significantly reduced by pre-treatment of the extract in a dose-dependent manner measured 9 h after UVB irradiation. The results suggest that the A. chinensis extract may have a protective effect on the UVB-injured keratinocytes by inhibiting PGE2 and NO production, possibly through the inhibition of intracellular ROS accumulation.

3beta,6beta-dihydroxyolean-12-en-27-oic acid: a cytotoxic and apoptosis-inducing oleanane triterpenoid from the rhizome of Astilbe chinensis.

3beta,6beta-dihydroxyolean-12-en-27-oic acid, C(30)H(48)O(4), a cytotoxic and apoptosis-inducing oleanane triterpenoid, which was isolated from the rhizome of Astilbe chinensis, consists of a linear array of five fused six-membered rings. The central ring has a slightly distorted half-chair conformation, while the four outer rings adopt chair conformations. Two hydroxy groups and one carboxy group serve simultaneously as hydrogen-bond donors and acceptors, forming molecular chains.