Kitja Sawangjaroen

The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.)

AIM OF THE STUDY The effects of pure alkaloid, mitragynine and a methanolic extract of kratom leaves were investigated on neuromuscular junction and compound nerve action potential. MATERIALS AND METHODS Wistar rats were killed by cervical dislocation and decapitated. The phrenic nerve-hemidiaphragms, hemidiaphragms and sciatic nerve were isolated. RESULTS Kratom methanolic extract present at 0.1-1 mg/mL and mitragynine (0.0156 mg/mL) decreased the muscle twitch on the isolated phrenic nerve-hemidiaphragm and hemidiaphragm preparation. Muscle relaxation caused by kratom extract (1 mg/mL) was greater than the effect of mitragynine. Pancuronium and succinylcholine potentiated the effect of kratom extract. It also had a direct relaxation effect on the hemidiaphragm muscle. The muscle relaxation caused by kratom extract was not antagonized by neostigmine, tetraethylammonium and calcium chloride. High concentrations of kratom extract (10-40 mg/mL) and mitragynine (2 mg/mL) blocked the nerve conduction, amplitude and duration of compound nerve action potential. CONCLUSIONS The mechanism of action of kratom extract might not act as a competitive antagonist of acetylcholine yet its dominant effect was at the neuromuscular junction and not at the skeletal muscle or somatic nerve.

Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract

Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine.

Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine

The leaves of Mitragyna speciosa Korth (Rubiaceae) have been used in folk medicine for its unique medicinal properties. This study examined the water, methanolic and crude alkaloidal extracts from M. speciosa leaves and its major constituent mitragynine for the enhancement of glucose transport. Cellular uptake of radioactive 2-deoxyglucose was determined in rat L8 myotubes. Involving signalling pathway was determined with the specific inhibitors. Cell cytotoxicity was monitored by lactate dehydrogenase assay. Protein levels of glucose transporters (GLUTs) were measured by Western blotting. The results show that test samples significantly increased the rate of glucose uptake. The uptake was associated with increase in GLUT1 protein content. Co-incubation with insulin had no additional effect, but the cellular uptake was decreased by wortmannin and SB 203580, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK), respectively. It is concluded that the increased glucose transport activity of M. speciosa is associated with increases in activities of the key enzymes dependent to the insulin-stimulated glucose transport for its acute action, and increases in the GLUT1 content for its long-term effect. This study demonstrated the effect of M. speciosa in stimulating glucose transport in muscle cells, implicating the folkloric use of M. speciosa leaves for treating diabetes.

Young coconut juice can accelerate the healing process of cutaneous wounds

BackgroundEstrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats.MethodsFour groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β) antibodies.ResultsWound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group.ConclusionsThis study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

Effects of an alkaloid-rich extract from Mitragyna speciosa leaves and fluoxetine on sleep profiles, EEG spectral frequency and ethanol withdrawal symptoms in rats.

BACKGROUND Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance. METHODS Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms. RESULTS The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity. CONCLUSION The present study demonstrated that the alkaloid extract from MS alleviates ethanol withdrawal severity with no side effect on REM sleep. In addition, these data suggest that suppressive effects on slow frequency powers but not REM sleep may be hallmarks of effective antidepressants for ethanol withdrawal treatment.