Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.

The hyperpolarization-activated cation current (Ih) exhibits a slowly activating time course of the current (Ih) when the cell membrane is hyperpolarized for an extended duration. It is involved in generating electrical activity in various excitable cells. Numerous structurally distinct compounds or herbal drugs have the potential to impact both the magnitude and gating kinetics of this current. Brivaracetam, a chemical analog of levetiracetam known to be a ligand for synaptic vesicle protein 2A, could directly suppress the Ih magnitude. Carisbamate, an anticonvulsant agent, not only inhibited the Ih amplitude but also reduced the strength of voltage-dependent hysteresis (Hys(V)) associated with Ih. Cilobradine, similar to ivabradine, inhibited the amplitude of Ih; however, it also suppressed the amplitude of delayed-rectifier K+ currents. Dexmedetomidine, an agonist of α2-adrenergic receptor, exerted a depressant action on Ih in a concentration-dependent fashion. Suppression of Ih amplitude was observed when GAL-021, a breathing control modulator, was present at a concentration exceeding 30 µM. Lutein, one of the few xanthophyll carotenoids, was able to suppress the Ih amplitude as well as to depress Hys(V)'s strength of Ih. Pirfenidone, a pyridine derivative known to be an anti-fibrotic agent, depressed the Ih magnitude in a concentration- and voltage-dependent fashion. Tramadol, a synthetic centrally active analgesic, was shown to reduce the Ih magnitude, independent of its interaction with opioid receptors. Various herbal drugs, including ent-kaurane-type diterpenoids from Croton tonkinensis, Ganoderma triterpenoids, honokiol, and pterostilbene, demonstrated efficacy in reducing the magnitude of Ih. Conversely, oxaliplatin, a platinum-based chemotherapeutic compound, was observed to effectively increase the Ih amplitude. Collectively, the regulatory effects of these compounds or herbal drugs on cellular function can be partly attributed to their perturbations on Ih.

Antioxidant activity and anticancer effect of ethanolic and aqueous extracts of the roots of Ficus beecheyana and their phenolic components.

This study aimed to investigate the antioxidant and anticancer effects of ethanolic and aqueous extracts of the roots of Ficus beecheyana (EERFB and AERFB) and their phenolic components. In this study, total phenolic content and antioxidant activity of EERFB were higher than those of AERFB. Major phenolic compounds in the extracts were gallic acid, p-hydroxybenzoic acid, caffeic acid, chlorogenic acid, p-coumaric acid, and rutin; which were identified by high-performance liquid chromatography. Flow cytometric analysis of HL-60 cells exposed to EERFB showed that the percentage of apoptotic cells increased in a dose-dependent manner. EERFB treatment resulted in the loss of mitochondrial membrane potential and induced the apoptosis of HL-60 cells through a Fas- and mitochondrial-mediated pathway. Finally, pretreatment with general caspase-9/-3 inhibitors prevented EERFB from inhibiting cell viability in HL-60 cells. Our finding suggests that EERFB is an agent that may have antioxidant activity and inhibit the growth of cancer cells.

The efficacy and safety of transnasal butorphanol for postoperative pain control following lower laparoscopic surgery.

BACKGROUND: The aim of the study was to evaluate the efficacy and safety of transnasal butorphanol for postoperative analgesia in adult female patients undergoing lower laparoscopic surgery. METHODS: Fifty-six women undergoing lower laparoscopic surgery under general anesthesia were enrolled in the study. They were randomly divided into 2 groups (n = 28 each). Postoperatively, group 1 received transnasal butorphanol 2 mg, whereas group 2 received transnasal placebo. During a 6-h post-treatment period, we collected the following data: scores of visual analogue pain scale, demand and delivery of patient-controlled analgesia (PCA) morphine, vital signs, nausea, vomiting, and somnolence. RESULTS: Transnasal butorphanol clearly proved to have analgesic effect when compared with placebo as revealed by diminishment of visual analogue scale scores at 30 min (P = 0.043), less consumption of PCA morphine at 30-60 min (P = 0.002), and less demand of PCA morphine at 30-60 min (P = 0.001) and 60-180 min (P = 0.031). All patients displayed stable vital signs. The side effects between groups were not significantly different. CONCLUSIONS: In contrast with placebo transnasal butorphanol was effective in the treatment of postoperative pain in female patients undergoing lower laparoscopic surgery. It had minimum side effects.