Identification and characterization of potential antioxidant components in Isodon amethystoides (Benth.) Hara tea leaves by UPLC-LTQ-Orbitrap-MS.

Isodon amethystoides (Benth.) Hara (IA) tea is a commonly used dietetic Chinese herb and employed for the treatments of tumor and lung abscess. To assess chemical composition and antioxidant capacity of IA leaves extract, a UPLC-LTQ-Orbitrap-MS method and antioxidant tests were used, respectively. 17 compounds were identified including Vinyl caffeate (1), 3,4-dimethoxyphenyl-ß-D-glucopyranoside (2), Rutin (3), Quercetin (4), Loliolide (5), Caffeic acid (6), Rubesanolide D (7), Isorhamnetin (8), Lambertic acid (9), 6, 7-Dehydroroyleanone (10), Dihydrorabdokunmin C (11), Nervosin (12), Quercitrin (13), Vitexin (14), ß-sitosterol (15), Wangzaozin A (16), Amethystonoic acid (17). Among these, 1-14 compounds were novel and have not been reported ever before in IA while component 10 was a novel finding within this genus. Flavonoid components showed better free radical scavenging ability and profound correlation was observed between diterpenoid compounds content and flavonoids activity. Our results provide experimental basis for extraction and separation of chemical constituents of IA which are antioxidant in nature.

Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials.

Background Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

Research Progress of Raman Spectroscopy in Drug Analysis.

Raman spectroscopy is a spectroscopic analysis technique that enables rapid qualitative and quantitative detection based on inelastic collision and Raman scattering intensity. This review detailed the generation principle, instrument composition, influencing factors, and common classifications of Raman spectrum. Furthermore, it summarized and forecast the research progress of Raman spectroscopy in the field of drug analysis simultaneously over the past decade, including the identification of active pharmaceutical ingredients (APIs), qualitative and quantitative studies of pharmaceutical preparations, detection of illicit drugs, the identification of Chinese herbal medicines, and the combination with other technologies. The development of Raman spectroscopy in other fields is additionally summarized.

Bioactivities and Chemical Constituents of Essential Oil Extracted from Artemisia anethoides Against Two Stored Product Insects.

The chemical constituents of the essential oil extracted from Artemisia anethoides and the bioactivities of essential oil against Tribolium castaneum and Lasioderma serricorne were investigated. The main components of the essential oil were 1,8-cineole (36.54%), 2-isopropyl-5-methyl-3-cyclohexen-1-one (10.40%), terpinen-4-ol (8.58%), 2-isopropyltoluene (6.20) and pinocarveol (5.08%). The essential oil of A. anethoides possessed contact and fumigant toxicities against T. castaneum adults (LD50 = 28.80 µg/adult and LC50 = 13.05 mg/L air, respectively) and against L. serricorne (LD50 = 24.03 µg/adult and LD50 = 8.04 mg/L air, respectively). The crude oil showed repellent activity against T. castaneum and L. serricorne. Especially, the percentage repellency of essential oil was same level with DEET (positive control) against T. castaneum. The results indicated that the essential oil of A. anethoides had the potential to be developed as insecticide and repellent for control of T. castaneum and L. serricorne.

Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation.

Tissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times. However, its underlying cellular mechanisms have remained elusive. The present study demonstrated for the first time that gastrodin exhibits an analgesic effect at the spinal level on spontaneous pain, mechanical and thermal pain hypersensitivity induced by peripheral inflammation, which is not dependent on opioid receptors and without tolerance. This analgesia by gastrodin is at least in part mediated by depressing spinal synaptic potentiation via blockade of acid-sensing ion channels. Further studies with miniature EPSCs and paired-pulse ratio analysis revealed the presynaptic origin of the action of gastrodin, which involves a decrease in transmitter release probability. In contrast, neither basal nociception nor basal synaptic transmission was altered. This study revealed a dramatic analgesic action of gastrodin on inflammatory pain and uncovered a novel spinal mechanism that could underlie the analgesia by gastrodin, pointing the way to a new analgesic for treating chronic inflammatory pain.

Contrasts between the phylogeographic patterns of chloroplast and nuclear DNA highlight a role for pollen-mediated gene flow in preventing population divergence in an East Asian temperate tree.

Plant phylogeographic studies in East Asia have provided support for the biogeographic hypothesis that the complex landforms and climate of this region have provided substantial opportunities for allopatric speciation. However, most of these studies have been based on maternally inherited chloroplast DNA (cpDNA) markers and were therefore unable to reveal the role of pollen-mediated gene flow in preventing population divergence. Here, we investigate the phylogeography of the Chinese walnut Juglans cathayensis, a temperate deciduous tree widely distributed across disjunct montane sites in subtropical China. We genotyped 19 populations using seven cpDNA fragments and ten nuclear microsatellite loci and modeled the ecological niche of J. cathayensis. CpDNA analysis identified a total of nine haplotypes, and each of the 19 sampled populations was fixed for a single haplotype, displaying a prominent phylogeographic structure. The results of ecological niche modeling indicated that J. cathayensis populations survived the last glaciation in situ, although they were probably more fragmented than today. In contrast, we detected a much weaker, but nonetheless clear, genetic structure based on nuclear microsatellite data. Our study demonstrates how extensive pollen flow can erase the genetic imprint of long-term refugial isolation in maternal lineages, effectively preventing population differentiation in temperate, particularly wind-pollinated, forest trees in subtropical China.

Zhuanggu Jianxi Decoction () limits interleukin-1 ß-induced degeneration chondrocytes via the caveolin-p38 MAPK signal pathway.

OBJECTIVE: To evaluate the effect of Zhuanggu Jianxi Decoction (, ZGJXD) on interleukin-1 ß (IL-1 ß)-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis. METHODS: Serum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL-1 ß stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II collagen immunocytochemistry. After IL-1 ß-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 ß, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 were examined by real-time polymerase chain reaction. RESULTS: IL-1 ß stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 ß, TNF-α, MMP-3 and MMP-13. However, the IL-1 ß-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs. CONCLUSION: ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.

[Effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe containing serum on caveolin-p38MAPK signal pathway in IL-1ß induced rabbit degenerated chondrocytes].

OBJECTIVE: To observe the effect of naringin of Drynaria Rhizome, a Chinese medical component of Zhuanggu Jianxi Recipe (ZJR) containing serum on caveolin-p38MAPK signal factors (such as caveolin-1, p-p38, p-ATF-2, IL-1ß, and TNF-α) in IL-1ß induced rabbit degenerated chondrocytes, and further to explore its mechanism for protecting articular cartilages. METHODS: Naringin of Drynaria Rhizome was obtained and analyzed by HPLC-TOF/MS. Four weeks old New Zealand rabbits were killed and their bilateral knee joints were isolated aseptically. CDs were isolated and then cultured in vitro. The second generation of CDs were used for later experiment. The effect of naringin on CDs proliferation was detected by MTT assay. The effect of naringin on the expression of IL-1ß-induced collagen II in CDs was detected by immunohistochemical method. The effect of naringin on caveolin-1, p-p38, and p-ATF-2 protein in IL-1ß-induced CDs was detected by Western blot. The effect of naringin on mRNA expression of IL-1ß and TNF-α in IL-1ß-induced CDs was detected by RT-PCR. RESULTS: The appearance time of naringin in flow graphs of naringin standard solution and ZJR containing serum was 23.5 min, and the molecular weight ranged between 581.0 and 581.5 m/z. Naringin could promote the proliferation of CDs, and inhibit the effect of IL-1ß on collagen II in CDs. Compared with the model group, naringin could reduce the expression of caveolin-1, p-p38, p-ATF-2, IL-1ß, and TNF-α in IL-1ß induced CDs (P < 0.05), which was approximate to the level of the normal group. CONCLUSIONS: Naringin could not only promote the proliferation of CDs, but also protect IL-1ß-induced CDs. Its mechanism might be associated with decreasing the expression of caveolin-1, p-p38, and p-ATF-2 proteins, inhibiting caveolin-p38MAPK signal pathway, and further reducing mRNA expression of IL-1ß and TNF-α in the downstream of caveolin-p38MAPK signal pathway.

Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I(NaT)) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I(NaT) and a decrease of potassium currents, especially slowly inactivating potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(NaT) and total potassium current as well as I(AS) currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN.

[Selective innervation of sacral anterior rootlets to micturition and erection function in rats].

OBJECTIVE: To investigate the selective innervation of sacral anterior rootlets to micturition and erection function in SD rats. METHODS: Forty male SD rats of clean grade, aged 6 weeks old, were selected. Ten rats received a retrograde nerve tract tracing study. Thirty rats were chosen for an electro-physiological study. The L6, S1 spinal cord segment anterior rootlets of anesthetic rats were electrostimulated respectively. The intravesical pressure, urethral perfusion pressure and intracavernous pressure were recorded simultaneously and innervation effectiveness was analyzed. RESULTS: CB-HRP labeled neurons were observed mainly in L6 and S1 spinal cords. When some anterior rootlets of L6 and S1 were electrostimulated, the intravesical pressure rose gradually, but the urethral perfusion pressure and the intracavernous pressure curve changed slightly; when other rootlets of the same anterior root were stimulated, the urethral perfusion pressure could reach the peak; while others were stimulated, the intracavernous pressure rose quickly, but there were no great changes in intravesical pressure and urethral perfusion pressure. Some other rootlets might lead to the simultaneous changes of 2 or 3 above-mentioned pressures. CONCLUSION: The innervations of L6 and S1 anterior rootlets to rats' bladder detrusor, external urethral sphincter and penile cavernous body are significantly distinct. Different rootlets may be distinguished by microanatomy and electrostimulation.

[Effects of highly selective dorsal rootlets rhizotomy on bladder function and penis erection in SD rats].

OBJECTIVE: To study the highly selective dorsal rhizotomy influence on bladder and penis erection function of SD rats. METHODS: Forty mature male SD rats of clean grades, with weight range of 300-350 g were selected. Ten rats were chosen to do electrophysiology study on dorsal rootlets of L6 and S1 segment. Changes in intravesical pressure (IVP) and intracavernous pressure (ICP) were investigated to define main segments which conducted to bladder and corpus cavernosum. Thirty rats were divided into two groups (A and B) on average at random. In group A, we made highly selective dorsal rhizotomy on the fascicle of conduction bladder detrusor muscle. In group B, we made highly selective dorsal rhizotomy on the fascicle of conduction corpus cavernosum. Changes of IVP and ICP after rhizotomy were investigated and recorded. RESULTS: The changes of IVP during electrostimulation were of no significant variation between L6 and S1 (P=0.972). With the changes of ICP during electrostimulation, S1 segment was of more significant variation than L6 segment, ΔICP of S1 was (13.05±8.41) cmH2O (1 cmH2O=0.098 kPa), while ΔICP of L6 was (6.88±2.76) cmH2O (P<0.01). There was no reasonable variation in IVP and ICP on the left and right dorsal rootlets of S1 segment (P was 0.623 and 0.828 respectively). In group A, there was significant variation in IVP, ΔIVP of before rhizotomy was (14.37±4.89) cmH2O, while after rhizotomy was (3.25±1.29) cmH2O (P<0.001) while no obvious variation in ICP (P=0.153) after highly selective rhizotomy on S1 dorsal rootlets. In group B, there was significant variation in ICP, ΔICP of before rhizotomy was (11.97±4.41) cmH2O, while after rhizotomy was (2.68±1.01) cmH2O (P<0.001), but no obvious variation in IVP (P=0.162) after highly selective rhizotomy on S1 dorsal rootlets. CONCLUSION: SD rats' different rootlets of S1 dorsal rootlets can be distinguished by microanatomy and electrostimulation. The IVP and ICP had distinct changes after highly selective dorsal rhizotomy. It could provide an experimental support to treat spastic bladder after spinal cord injury and retain at maximum reflexible erection function in the clinic.