OBJECTIVETo investigate the chemical constituents from Lamiophlomis rotata and the bioactivities of 8-epideoxyloganic acid.

METHODThe constituents were isolated by using a combination of various chromatographic techniques including column chromatography over ployamide, silica gel and Sephadex LH-20. Structures of the isolates were identified by spectroscopic data analysis. Bioactivities were screened by using models in vivo.

RESULTFive constituents were isolated. 8-epideoxyloganic acid was isolated for the first time in L. rotata and also in lamioplomis genus. 8-epideoxyloganic acid could significantly inhibit aectic acid-induced twisting times and slower the time of homeostatsis, also inhibit xylene-induced ear edema in mice.

CONCLUSION8-epideoxyloganic acid possesses bioactivities of analgesia, homeostasis and anti-inflammatory.

Analgesics ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Female ; Lamiaceae ; chemistry ; Male ; Mice ; Pyrans ; isolation & purification ; pharmacology

AIM: To determine the IPP origin of the naphthoquinones (NQs) in Rubia cordifolia, and to evaluate the effects of methyl jasmonate (MeJA) treatment, MEP, and MVA pathway inhibitor treatment on the accumulation of anthraquinones (AQs) and NQs in cell suspension cultures of R. cordifolia. METHODS: Cell suspension cultures of R. cordifolia were established. Specific inhibitors (lovastatin and clomazone) and MeJA were supplied to the media, respectively. Treated cells were sampled every three days. Content determination of purpurin (AQs) and mollugin (NQs) were carried out using RP-HPLC. The yield of the two compounds was compared with the DMSO-supplied group and the possible mechanism was discussed. RESULTS: Lovastatin treatment increased the yield of purpurin and mollugin significantly. Clomazone treatment resulted in a remarkable decrease of both compounds. In the MeJA-treated cells, the purpurin yield increased, meanwhile, the mollugin yield decreased compared with control. CONCLUSION The IPP origin of mollugin in R. cordifolia cell suspension cultures was likely from the MEP pathway. To explain the different effects of MeJA on AQs and NQs accumulation, studies on the regulation and expression of the genes, especially after prenylation of 1,4-dihydroxy-2-naphthoic acid should be conducted.
Acetates ; pharmacology ; Anthraquinones ; metabolism ; Cell Culture Techniques ; Cells, Cultured ; Cyclopentanes ; pharmacology ; Isoxazoles ; pharmacology ; Lovastatin ; pharmacology ; Oxazolidinones ; pharmacology ; Oxylipins ; pharmacology ; Pyrans ; metabolism ; Rubia ; drug effects ; metabolism

Host cell protein phosphatase-1 (PP1) is an important regulator of human immunodeficiency virus-1 (HIV-1) transcription. PP1 is involved in the regulation of HIV-1 transcription, and dephosphorylates RNA polymerase II C-terminal domain (RNAPII CTD) or CycT1-dependent kinase 9 (CDK9) to increase Tat-dependent HIV-1 transcription. In this review, we discuss the action of PP1 in Tat-induced HIV-1 transcription and related to PP1 inhibitors.
Anti-HIV Agents ; pharmacology ; Enzyme Inhibitors ; pharmacology ; HIV-1 ; genetics ; Humans ; Okadaic Acid ; pharmacology ; Protein Phosphatase 1 ; antagonists & inhibitors ; chemistry ; physiology ; Pyrans ; pharmacology ; Spiro Compounds ; pharmacology ; Transcription, Genetic ; tat Gene Products, Human Immunodeficiency Virus ; physiology

This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.
Animals ; Benzopyrans/*pharmacology ; Cromakalim ; Guanidines/*pharmacology ; Muscle Contraction/drug effects ; Muscle, Smooth/*drug effects ; Picolines/*pharmacology ; Potassium Channels/*drug effects ; Pyrans/*pharmacology ; Pyrroles/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder/*drug effects/physiology

The advances in the research on pharmacological activities of aucubin have been summarized in the last ten years. Aucubin is one of active components of Chinese medicinal herbs such as Eucommia ulmoides and has been shown wide pharmacological activities including hepatoproective, antitoxicanti-inflammatory, antioxidant, antiaging, antiosteoporosis and neurotrophic and should be further researched and utilized.
Aging ; drug effects ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Antioxidants ; pharmacology ; Eucommiaceae ; chemistry ; Glucosides ; chemistry ; isolation & purification ; pharmacology ; Iridoid Glucosides ; Iridoids ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Plants, Medicinal ; chemistry ; Pyrans ; chemistry ; isolation & purification ; pharmacology

OBJECTIVETo investigate the protective effect of geniposide, baicalin and berberine for the rat cerebral microvascular endothelial cell.

METHODThe model of hypoxia and reoxygenation injury in rat cerebral microvascular endothelial cells in vitro was established. Both normal and model cells were treated with geniposide (1.024, 0.512, 0.256, 0.128, 0.064, 0.032, 0.016, 0.008 micromol x mL(-1)), baicalin (0.224, 0.112, 0.056, 0.028, 0.014, 0.007, 0.003 micromol x mL(-1)) and berberine (0.192, 0.096, 0.048, 0.024, 0.012, 0.006, 0.003 micromol x mL(-1)). Cell activity was measured by methyl thiazolyl tetrazolium (MTT) test.

RESULTAfter hypoxia/hypoglycemia cultures for 4 hour and reoxygenation for 12 hour, geniposide (0.128, 0.064, 0.032 micromol x mL(-1)), baicalin (0.028, 0.014, 0.007 micromol x mL(-1)) and berberine (0.024, 0.012, 0.006 micromol x microL(-1) could protect the injuried cerebral microvascular endothelial cells.

CONCLUSIONAppropriate concentration of geniposide, baicalin and berberine, which are effective components of Huanglian Jiedu decoction, could protect the injuried cerebral microvascular endothelial cells.

Animals ; Berberine ; isolation & purification ; pharmacology ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Cerebral Cortex ; blood supply ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; Endothelial Cells ; cytology ; drug effects ; Flavonoids ; isolation & purification ; pharmacology ; Iridoids ; isolation & purification ; pharmacology ; Male ; Neuroprotective Agents ; pharmacology ; Oxygen ; pharmacology ; Plants, Medicinal ; chemistry ; Pyrans ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley

To study whether commercial traditional Chinese medicinal preparations Injection Paederiae (IP) or Injection Stauntonia (IS) has anti-nociceptive and/or anti-inflammatory effects, we used two persistent pain models (bee venom and formalin test) to evaluate the systemic effects of IP or IS on the chemical tissue injury-induced persistent spontaneous pain-related responses (PSPR), primary thermal/mechanical hyperalgesia and inflammation in conscious rats. Injection of bee venom (BV, 0.1 mg, 50 microl) into the plantar surface of one hind paw resulted in not only a 1-h monophasic PSPR such as flinching reflex in the injected paw and a subsequent period of 3-4 days primary heat and mechanical hyperalgesia, but also a marked sign of inflammation, including redness and swelling of the plantar surface in the injected paw. Intraplantar injection of formalin produced two phases of PSPR as reported previously. Systemic pre-treatment with three doses of IP (0.32, 1.6 and 9.0 ml/kg, 500%) or IS (0.32, 1.6 and 9.0 ml/kg, 250%) produced a dose-dependent suppression of the BV- or formalin-induced flinching reflex of 1 h time course as compared with the saline control group. Post-treatment with IP or IS 5 min after BV injection also produced a significant suppression of the flinching reflex in both BV test and formalin test respectively, as compared with the control group. However, neither pre- nor post-treatment with IP or IS produced any significantly suppressive effect on the BV-induced primary heat and mechanical hyperalgesia and inflammation. The analgesia produced by IP or IS was not mediated by the endogenous opioid receptors since naloxone, a non-selective opioid receptor antagonist, had no reversal effect on the IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest that IP or IS might prevent and relieve clinical persistent spontaneous pain, but without any anti-nociceptive and anti-inflammatory effects on the primary heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses. The BV test might be a useful model of pain to evaluate and screen anti-nociceptive and anti-inflammatory effects of certain compounds of the Chinese medicinal herbs on the pathological origins of pain.
Analgesics ; pharmacology ; Animals ; Bee Venoms ; Drugs, Chinese Herbal ; pharmacology ; Female ; Formaldehyde ; Hyperalgesia ; physiopathology ; Inflammation ; chemically induced ; physiopathology ; Injections, Intravenous ; Male ; Nociceptors ; drug effects ; Pain ; chemically induced ; physiopathology ; Pain Threshold ; drug effects ; Pyrans ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Steroids ; pharmacology

OBJECTIVE: To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms. METHODS: We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor). RESULTS: In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis. CONCLUSIONS ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.
Acetates ; pharmacology ; Apoptosis ; drug effects ; genetics ; Autophagy ; drug effects ; Autophagy-Related Proteins ; metabolism ; Benzopyrans ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation ; Humans ; MCF-7 Cells ; Morpholines ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; metabolism ; Pyrans ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Triazines ; pharmacology ; Ubiquitin-Conjugating Enzymes ; metabolism

We previously reported that the p53 tumor suppressor protein plays an essential role in the induction of tetraploid G1 arrest in response to perturbation of the actin cytoskeleton, termed actin damage. In this study, we investigated the role of p53, ataxia telangiectasia mutated protein (ATM), and catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in tetraploid G1 arrest induced by actin damage. Treatment with actin-damaging agents including pectenotoxin-2 (PTX-2) increases phosphorylation of Ser-15 and Ser-37 residues of p53, but not Ser-20 residue. Knockdown of ATM and DNA-PKcs do not affect p53 phosphorylation induced by actin damage. However, while ATM knockdown does not affect tetraploid G1 arrest, knockdown of DNA-PKcs not only perturbs tetraploid G1 arrest, but also results in formation of polyploidy and induction of apoptosis. These results indicate that DNA-PKcs is essential for the maintenance of actin damage induced-tetraploid G1 arrest in a p53-independent manner. Furthermore, actin damage-induced p53 expression is not observed in cells synchronized at G1/S of the cell cycle, implying that p53 induction is due to actin damage-induced tetraploidy rather than perturbation of actin cytoskeleton. Therefore, these results suggest that p53 and DNA-PKcs independently function for tetraploid G1 arrest and preventing polyploidy formation.
Actins/*metabolism ; Apoptosis ; Catalytic Domain ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; DNA-Activated Protein Kinase/chemistry/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Furans/pharmacology ; *G1 Phase ; Gene Knockdown Techniques ; Humans ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Pyrans/pharmacology ; Tumor Suppressor Protein p53/*metabolism ; Tumor Suppressor Proteins/genetics/*metabolism

OBJECTIVETo study the effect of geniposide on serum IL-1beta and TNF-alpha levels of rheumatoid arthritis rats, as well as the mechanism of this drug.

METHODTo establish an experimental rat model of type II collagen-induced arthritic (CIA). The inhibitory effects on paw edema were observed, and serum IL-1beta and TNF-alpha levels were determined in experimental rats.

RESULTCompared with the model, geniposide delayed the starting time of right paw edema significantly, and the levels of serum IL-1beta and TNF-alpha were significantly decreased by geniposide at high dose or medium dose (P < 0.01).

CONCLUSIONGeniposide can lower serum IL-1beta and TNF-alpha levels in rheumatoid arthritis rats. The effect may be close related to inhibitory development of rheumatoid arthritis by the agent.

Animals ; Arthritis, Rheumatoid ; blood ; chemically induced ; pathology ; Collagen Type II ; Dose-Response Relationship, Drug ; Edema ; chemically induced ; pathology ; Gardenia ; chemistry ; Hindlimb ; pathology ; Interleukin-1 ; blood ; Iridoids ; administration & dosage ; isolation & purification ; pharmacology ; Male ; Plants, Medicinal ; chemistry ; Pyrans ; administration & dosage ; isolation & purification ; pharmacology ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; metabolism