Ophiopogon japonicus, a precious medicinal plant endemic to Zhejiang Province. Its tuberous roots are rich in bioactive components such as flavonoids, possessing anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the impact of cadmium (Cd) stress on the accumulation and biosynthetic pathway of flavonoids in O. japonicus, this study exposed O. japonicus to different concentrations of Cd stress and explored the changes through integrated transcriptomics and metabolomics analysis. The results demonstrated that Cd stress (1 mg/L and 10 mg/L) significantly increased the content of flavonoids in O. japonicus in a concentration-dependent manner. The metabolomics analysis revealed a total of 110 flavonoids including flavones, flavanols, flavonols, flavone and flavonol derivatives, flavanones, isoflavonoids, chalcones and dihydrochalcones, and anthocyanins in O. japonicus, among which flavones, flavonols, flavone and flavonol derivatives, and anthocyanins increased under Cd stress. The transcriptomics analysis identified several key flavonoid biosynthesis-associated genes with up-regulated expression under Cd stress, including 14 genes encoding 4-coumarate CoA ligase (4CL), 2 genes encoding chalcone isomerase (CHI), and 14 genes encoding phenylalanine ammonia lyase (PAL). The gene-metabolite regulatory network indicated significant positive correlations of 4CL (Cluster-21637.5012, Cluster-21637.90648, and Cluster-21637.62637) and CHI (Cluster-21637.111909 and Cluster-21637.123300) with flavonoid metabolites, suggesting that these genes promoted the synthesis of specific flavonoid metabolites, which led to the accumulation of total flavonoids under Cd stress. These findings provide theoretical support for the cultivation and utilization of medicinal plants in Cd-contaminated environments and offered new perspectives for studying plant responses to heavy metal stress.
Cadmium/toxicity* ; Flavonoids/biosynthesis* ; Metabolomics ; Ophiopogon/drug effects* ; Stress, Physiological ; Transcriptome ; Gene Expression Profiling ; Gene Expression Regulation, Plant

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

OBJECTIVE: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated. RESULTS: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). CONCLUSION CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
Alkaloids ; pharmacology ; Animals ; Apoptosis ; drug effects ; Atherosclerosis ; Diabetes Mellitus, Experimental ; Diabetic Angiopathies ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Male ; Ophiopogon ; chemistry ; Panax notoginseng ; chemistry ; Polysaccharides ; pharmacology ; Rabbits ; Saponins ; pharmacology

For understanding the effect of MDG-1, a water-soluble β-D-fructan polysaccharide from Ophiopogon japonicas, on intestinal microecological balance, especially on the changes of lactobacillus, sixty 8-week-old male C57BL/6J mice were given a high-fat diet for six weeks and were also gavaged with saline once a day simultaneously. Then the mice which is below 30 grams or dropped more than 10% through lavage were eliminated and the rest were randomly divided into four groups: diet-induced obese (DIO) model group (n = 12, gavaged with saline), low-dose MDG-1 group (n = 12, gavaged with MDG-1, 75 mg · kg(-1)) , medial-dose MDG- 1 group (n = 12, gavaged with 150 mg · kg(-1)), and high-dose MDG-1 group (n = 12, gavaged with 300 mg · kg(-1)) according to the weight and blood glucose; the model group and MDG-1 group were placed on a high-fat diet while the normal control group (n = 12, gavaged with saline) were kept on a low-fat diet through the experiment. After 12-weeks of treatment, feces samples were collected and cultured for intestinal microecological balance analysis. Then the intestinal probiotics were cultured through traditional methods combined with modified gradient gel electrophoresis (DGGE) method. The changes of lactobacillus in each treatment group were also detected by a statistical analysis of the total number of the intestinal flora. We have established the phylogenetic tree by 16S rDNA sequencing and use some molecular identification methods such as PCR-DGGE to analyse the changes of the dominant bacteria floras, and also get the pure culture. In conclusion, different concentrations of MDG-1 can increase the number of the intestinal probiotics, especially Taiwan lactobacillus and Lactobacillus murinus, and improve their diversity and promote proliferation in a dose-dependent way.
Animals ; Biodiversity ; Diet, High-Fat ; adverse effects ; Dietary Carbohydrates ; administration & dosage ; analysis ; Humans ; Intestines ; drug effects ; metabolism ; microbiology ; Lactobacillus ; classification ; drug effects ; genetics ; growth & development ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Molecular Structure ; Obesity ; drug therapy ; metabolism ; microbiology ; Ophiopogon ; chemistry ; Phylogeny ; Plant Extracts ; administration & dosage ; chemistry ; Polysaccharides ; administration & dosage ; chemistry

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.
Adenine ; analogs & derivatives ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; Beclin-1 ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Ophiopogon ; chemistry ; PTEN Phosphohydrolase ; metabolism ; Phosphorylation ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-akt ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Spirostans ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; Up-Regulation

OBJECTIVETo study the effects of the water extract of Rehmannia glutionsa, Scrophularia ningpoensis, Asparagus cochinchinensis and Ophiopogon japonicas, which are the drug from Tianwang Buxin Wan from nourishing vin, on the content of cytohrome P450 (CYP450) in rat and the activities of CYP3A, CYP2E1 and CYP1A2 to investigate the role of CYP450 in the biotransformation of Tianwang Buxin Wan.

METHODThe rats were killed after administrated with extracts once daily for consecutive 7 days, the livers were removed rapidly and weighed, liver microsomes were prepared with ultra-centrifuge method, the contents of liver microsomal CYP450, cytochrome b5 (Cytb5) and the activities of CYP3A were examined by ultraviolet spectrophotometry, the activities of CYP2E1 and CYP1A2 were determined by high performance liquid chromatography (HPLC).

RESULTAll groups had no difference in the levels of liver indexe compared with normal sodium group. The water extract of R. glutionsa obviously decreased the contents of P450 (P < 0.01) and increased the activity of CYP3A (P < 0.01) and CYP1A2 (P <0.05). The water extract of S. ningpoensis decreased the contents of P450 (P < 0.05) and significantly increased CYP3A and CYP1A2 activities (P < 0.01). A. cochinchinensis increased content of Cytb5 (P < 0.05) in rat and increased the activity of CYP2E1 (P < 0.05) and CYP1A2 (P < 0.01). O. japonicas had no significant difference on the contents of CYP450 and Cytb5 while increased the activities of CYP3A (P < 0.05), CYP2E1 (P < 0.05) and CYP1A2 (P < 0.01).

CONCLUSIONR. glutionsa and S. ningpoensis could decrease the content of CYP450 enzyme in rat liver and induct the activities of CYP3A and CYP1A2. A. cochinchinensis could induct the activities of CYP2E1 and CYP1A2. O. japonicus could induction the activities of CYP3A, CYP2E1 and CYP1A2 in Tianwang Buxin Wan. By inhibiting CYP450 activity to decrease the metabolism of other drugs, the effect of other functional groups in the compatibility of Tianwang Buxin Wan can be enhanced, and a theoretical basis on studying the compatible mechanism can be provided.

Animals ; Asparagus Plant ; chemistry ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP2E1 ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; Enzyme Activation ; drug effects ; Humans ; Liver ; drug effects ; enzymology ; Male ; Microsomes, Liver ; drug effects ; enzymology ; Ophiopogon ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rehmannia ; chemistry ; Scrophularia ; chemistry

OBJECTIVETo investigate the potential developmental toxicity of Radix Ophiopogonis decoction in SD rats.

METHODTimed-pregnant SD rats were given Radix Ophiopogonis decoction (26.9 g x kg(-1)) or vehicle (distilled water) by gavage on gestation days 6-17. Maternal clinical sign, abortions, premature deliveries, and body weight were monitored throughout gestation. At termination (gestation days 20) pregnant females were evaluated for clinical status and gestational outcome; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.

RESULTNo deaths, premature deliveries or dose-related clinical signs were attributed to Radix Ophiopogonis decoction. Maternal body weight and body weight gain were not affected. There were no effects on fetus weight and viability, incidences of fetal malformation and variation.

CONCLUSIONThese results demonstrated that Radix Ophiopogonis decoction had no detectable adverse effects in either the treated F0 female rats or the fetuses.

Animals ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Embryonic Development ; drug effects ; Female ; Fetal Development ; drug effects ; Fetal Weight ; drug effects ; Humans ; Male ; Models, Animal ; Ophiopogon ; chemistry ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate suitable oral absorption enhancer (s) for Ophiopogon japonicas polysaccharides (OJP) and provide bases of utilizing the absorption enhancer to realize the oral administration of OJP.

METHODThe absorption enhancement effects and cytotoxicity of clove oil, peppermint oil, borneol, Sanqi saponins, Maidong saponins, Ginseng saponin Rg1, Sanqi saponin R1 and sodium caprate (SC) were evaluated via Caco-2 cell culture model. The absorption of OJP from rat intestinal segments and the absorption enhancement effect of SC were investigated by in situ experiments of rat intestinal segments.

RESULTSC was an effective and safe absorption enhancer. However, the absorption enhancement effects of clove oil, peppermint oil and Maidong saponins were highly correlated with their cytotoxicity. OJP alone was poorly absorbed from all the rat intestinal segments. It was rapidly absorbed when co-administered with SC, and the absorption increase was significant and the best absorption enhancing site of SC for OJP was colon.

CONCLUSIONThe absorption enhancement effects of absorption enhancers are often correlated with their cytotoxicity. Co-administrating a powerful and safe absorption enhancer is an effective and valuable method of enhancing oral absorption of OJP.

Adjuvants, Pharmaceutic ; adverse effects ; Animals ; Caco-2 Cells ; Drug Delivery Systems ; methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Intestinal Absorption ; drug effects ; Male ; Ophiopogon ; chemistry ; Polysaccharides ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effects and the possible mechanism of shengmai for injection(SM) against the experimental acute cardiogenic shock.

METHODThe experimental acute cardiogenic shock model was established by ligating the anterior descending cornonary in dogs. The effects of SM on cardiogenic shock were investigated by measuring the hemodynamics parameter, the activity of LDH, CK, SOD and the contents of MDA in blood serum.

RESULTIn the dogs treated with SM, the mean arterial pressure (MAP), heart rate (HR), left ventricular pressure (LVP), the maximum of its first derivative (+/- dp/dtmax), the cardiac output (CO) and the cardiac index (CI) were increased significantly. The left ventricular end diastolic pressure (LVEDP) and the peripheral vascular resistance (TPVR) were decreased significantly, the myocardial infarct size was redused observely. In addition, the activity of LDH, CK and the contents of MDA in serum were decreased significantly, however the activity of SOD was increased observely.

CONCLUSIONThe results indicate that SM has the protective effects on cardiogenic shock.

Animals ; Cardiac Output ; drug effects ; Cardiotonic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Creatine Kinase ; blood ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; physiology ; Injections, Intravenous ; L-Lactate Dehydrogenase ; blood ; Male ; Malondialdehyde ; blood ; Myocardial Infarction ; pathology ; prevention & control ; Ophiopogon ; chemistry ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Schisandra ; chemistry ; Shock, Cardiogenic ; blood ; physiopathology ; prevention & control ; Vascular Resistance ; drug effects

OBJECTIVETo investigate the protective effect of Ophiopogonis polysaccharide (MDG-1) on isolated myocardium ischemia/reperfusion injury (IRI) and subcutaneous injection of isoprenaline induced acute myocardial ischemia.

METHODSIn ex vivo heart experiment: Langendorff guinea pigs were randomly divided into the IRI group, the fructose sodium diphosphate (FDP) group, treated with FDP 10(-6) - 10(-4) g/mL for positive control and the MDG groups treated with MDG-1 10(-6) - 10(-4) g/mL. The amplitude and frequency of cardiac contraction, coronary blood flow at different time points after ischemia reperfusion were measured. In integral animal experiments: acute myocardium ischemia model rats established by subcutaneous injection of isoprenaline were used, they were administered with MDG-1 in dosage of 10, 20 and 40 mg/kg respectively, and controlled with propranolol. Besides, a normal control group and an untreated model group for control were set up. The ST segment shift in ECG and lactate dehydrogenase (LDH) activity in serum were observed.

RESULTSEx vivo heart experiment showed that different doses of MDG-1 can increase IRI caused abnormal coronary blood flow, quickly resume the heart contraction and restrain the quickened heart rate (all P < 0.01). The integral animal experiment showed that oral administration of 40 mg/kg can reduce the increased activity of LDH in serum (P < 0.05) induced by isoprenaline, but almost had no effect on ST-segment shift in ECG.

CONCLUSIONMDG-1 can alleviate IRI isolated myocardium of guinea pigs, and oral administration of MDG-1 showed a definite protection on isoprenaline caused rats' myocardial ischemia damage.

Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Electrocardiography ; Guinea Pigs ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Isoproterenol ; Male ; Myocardial Contraction ; drug effects ; Myocardial Ischemia ; chemically induced ; drug therapy ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Ophiopogon ; chemistry ; Phytotherapy ; Plant Roots ; chemistry ; Polysaccharides ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley