Jatrorrhizine

J.Appl.Biol. Chem.,2011,54(2):.114-9.

Anti-inflammatory Effect of Jatrorrhizine from Phellodendron amurense in Lipopolysaccharide-stimulated Raw264.7 Cells.[Reference: WebLink]

n-Butanol extracts from Phellodendron amurense have about 50% inhibitory activity against hyaluronidase.
METHODS AND RESULTS:
The anti-inflammatory compound was isolated from P. amurense by Sephadex LH-20 and MCI-gel CHP-20 column chromatography with gradient elution. As a the result, its structure was identified as Jatrorrhizine by the interpretation of spectroscopic analyses including - and -NMR. In anti-inflammatory activity, the expression of nitric oxide (NO) was inhibited as above 60% at 100 concentration of extracts and then purified Jatrorrhizine from P. amurense. The inhibitory activities against the expression of inducible NO syntase (iNOS) and cyclooxygenase-2 (COX-2) were 45% and 29%.
CONCLUSIONS:
It seems that the extracts and purified Jatrorrhizine from P. amurense were expected anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated Raw264.7 cells.

Xenobiotica . 2019 Oct;49(10):1237-1243.

Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice[Pubmed: 30472912]

Abstract 1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that Jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether Jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters. 2. In vitro uptake tests showed that Jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 μM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1-1 μM (for OCT2 and OCT3) and 1-10 μM (for PMAT). 3. In mouse synaptosomes, Jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant. 4. The antidepressant-like action of Jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of Jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group. 5. The concentration of Jatrorrhizine shows a dose-dependent increase in brain tissues. 6. Our study suggested that Jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters. Keywords: Jatrorrhizine; antidepressant; organic cation transporter; plasma membrane monoamine transporter; uptake-2.

Phytomedicine. 2014 Sep 25;21(11):1373-81.

The antihypercholesterolemic effect of jatrorrhizine isolated from Rhizoma Coptidis.[Pubmed: 24894270]

METHODS AND RESULTS:
Current work was conducted to evaluate the safety and antihypercholesterolemic activity of Jatrorrhizine extracted from Rhizoma Coptidis (RC) and its potential mechanism on regulating cholesterol metabolism. It was found that the LD50 of Jatrorrhizine in mice was more than 5,500 mg/kg and there were no influences on clinical signs, organ weight changes, urinalysis and hematological parameters, gross necropsy and histological alterations in Jatrorrhizine-treated rats during the 3-month period, compared to the control group. Jatrorrhizine showed a strong lipid-lowering effect in a dose-dependent manner. Oral administration of 70.05 mg/kg of Jatrorrhizine on Mesocricetus auratus (Syrian golden hamsters) exhibited significant decrease in TC, TG, and LDL-c levels by 20%, 43%, and 19%, respectively, and increase in HDL-c and total bile acids (TBA) content in feces (p<0.01), compared to high-fat and high-cholesterol (HFHC) group. Besides, Jatrorrhizine dose-dependently slowed the rate of weight gain. The results of qRT-PCR, western blotting and ELISA revealed that Jatrorrhizine significantly up-regulated the mRNA and protein expression of LDLR and CYP7A1, but exhibited no significant effect on mRNA and protein expression of HMGR and ASBT in hamsters.
CONCLUSIONS:
In conclusion, Jatrorrhizine was a safe and potential antihypercholesterolemic agent from RC which could improve the utilization and excretion of cholesterol by up-regulating the mRNA and protein expression of LDLR and CYP7A1.

J. Pharm. Pharmacol., 2012, 64(3):413-9.

Effect of jatrorrhizine on delayed gastrointestinal transit in rat postoperative ileus.[Pubmed: 22309273 ]

Postoperative ileus is major cause of postoperative complication and prolonged hospitalization. Jatrorrhizine, which is a protoberberine alkaloid isolated from the medicinal plants Berberis aristata and Coptis chinensis, has been found to increase contractility of gastric antral and ileum smooth muscles of rat gastrointestinal tract. We have investigated whether Jatrorrhizine could offset gastrointestinal transit in rat with postoperative ileus.
METHODS AND RESULTS:
Postoperative ileus was induced by laparotomy with intestinal manipulation under anaesthesia. Gastrointestinal transit was evaluated by measurement of gastric emptying, geometric centre and the migration of Evans blue. Postoperative ileus significantly delayed gastric emptying and intestinal transit. Jatrorrhizine dose-dependently (0.1, 0.3 and 1 mg/kg) offset delayed gastric emptying and intestinal transit (geometric centre and the migration of Evans blue) in postoperative ileus. Pretreatment of animals with atropine inhibited the action of Jatrorrhizine on gastric emptying and intestinal transit, but pretreatment of animals with SB204070 did not influence the effect of Jatrorrhizine on gastric emptying and intestinal transit in postoperative ileus.
CONCLUSIONS:
Jatrorrhizine offset postoperative ileus-induced delayed gastric emptying and intestinal transit in rats, an action mediated via the cholinergic pathway, but not involving activation of 5-HT(4) receptors.

Biopharm Drug Dispos. 2013 Apr;34(3):176-85.

CYP450 1A2 and multiple UGT1A isoforms are responsible for jatrorrhizine metabolism in human liver microsomes.[Pubmed: 23299247 ]

Jatrorrhizine, one of the protoberberine alkaloids derived from the plant Coptis chinensis, is expected to be developed as a new gastric prokinetic drug, but its metabolic characteristics in humans remain unknown.
METHODS AND RESULTS:
This study characterized the phase I and phase II metabolites, metabolic kinetics, and cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes responsible for the metabolism of Jatrorrhizine in human liver microsomes (HLMs). Chemical inhibition in HLMs and metabolism by recombinant human CYP or UGT enzymes were employed to determine the key metabolic enzyme subtypes. In HLMs, demethyleneberberine (demethylated product) and Jatrorrhizine glucuronide were identified as the phase I and phase II metabolites, respectively. The enzyme kinetics for both demethylation and glucuronidation were fitted to the Michaelis-Menten equation. Demethylation was inhibited significantly by furafylline and predominantly catalysed by recombinant CYP1A2, whereas glucuronidation was inhibited by silibinin, quercetin, as well as 1-naphthol and catalysed by recombinant UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9 and UGT1A10.
CONCLUSIONS:
These results showed that Jatrorrhizine is metabolized by human CYP1A2 and multiple UGT1A isoforms.

Chinese Traditional & Herbal Drugs, 2005, 36(4):548-51.

Effect of jatrorrhizine, berberine, Huanglian Decoction and compound-mimic prescription on blood glucose in mice.[Reference: WebLink]

To study the hypoglycemic activity of Jatrorrhizine (Jat) and compare the effects of Jat, berberine (Ber), Huanglian Decoction (HLD), and compounds-mimic prescription (Ber+Jat) on blood glucose level in mice.
METHODS AND RESULTS:
TLC-scanning method was adopted for the determination of Ber and Jat in HLD. Ber+Jat was made artificially according to the result of the TLC-scanning. Diabetic model mice were made by ip alloxan, diabetic and normal mice were given Jat, Ber, HLD, and Ber+Jat in different dose by ig and applied in the study. Blood glucose level was analyzed by spectrophotometry with glucose-oxidase. Jat, Ber, HLD, and Ber+Jat decreased blood glucose level of diabetic and normal mice at different degrees. HLD showed the most significant hypoglycemic activity. Jat also possessed the function of decreasing blood glucose, which was less than that of Ber at the same dose. There was no significant difference between Ber+Jat and Ber.
CONCLUSIONS:
It implies that there are some other hypoglycemic ingredients in HLD besides Ber and Jat. Jat has no evident synergistic or antagonistic action when coexisted with Ber in natural ratio.