Palmatine hydrochloride

Acta Chim. Sin. Chinese Edition, 2009, 67(21):2511-6.

Investigation on the Anti-Candida albicans Effect of Palmatine Hydrochloride Based on Microcalorimetry and Principal Component Analysis[Reference: WebLink]

METHODS AND RESULTS:
Using an LKB-2277 bioactivity monitor, the metabolic power-time curves of Candida albicans (C albicans) growth affected by Palmatine hydrochloride were measured at 37 degrees C, then nine quantitative thermokinetic parameters were obtained from these curves and investigated by principal component analysis (PCA) to evaluate the anti-C. albicans effect of Palmatine hydrochloride. The results showed that the anti-C. albicans effect of this compound was mainly influenced by the growth rate constant (k(2)) and maximum power output P(m)(2) of phase II, and could be easily, quickly and exactly evaluated by analyzing the change of these two quantitative parameters.
CONCLUSIONS:
This work provides a useful method and idea for further evaluating the anti-bacterial effect of other drugs and compounds.

Proceedings of the National Academy of Sciences, 2014, 48(3):461-471.

Palmatine hydrochloride improves motor dysfunction in streptozotocin-induced diabetic rats.[Reference: WebLink]

Diabetes induces motor dysfunctions, Palmatine is an isoquinoline alkaloid, with anti-diabetic and antioxidant activities. This study was conducted to evaluate the effect of Palmatine on motor dysfunction in STZ-induced diabetic rats.
METHODS AND RESULTS:
In this experimental study, 32 male wistar rats were randomly allocated into control, Palmatine-treated non-diabetic, diabetic and Palmatine-treated diabetic groups. Diabetes was induced by STZ administration at the dose of 55 mg/kg/bw, intraperitoneally. Palmatine hydrochloride was administered subcutaneous at doses of 10 mg/kg/bw per day for a period of 6 weeks, one week after induction of diabetes. Blood glucose level was measured 1, 3, 5, 7 weeks after STZ injection. Locomotor activity tests including Y maze, grip-traction and inclined plane tests were performed to determining locomotor activity. Results: In Y maze test, the number of arms entered significantly increased in Palmatine-treated diabetic group compared to diabetic group (P<0.05). Grip traction and inclined plane tests significantly increased in Palmatine-treated diabetic group compared to diabetics animals (P<0.05).
CONCLUSIONS:
Palmatine hydrochloride administration for 6 weeks improves motor dysfunctions in streptozotocin-induced diabetic rats.

Pharmacol Res . 2018 Nov;137:34-46.

Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota[Pubmed: 30243842]

Abstract Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1) and the positive drug Sulfasalazine (SASP, 200 mg kg-1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis. Keywords: Gut microbiota; Palmatine; Tryptophan metabolism; Ulcerative colitis.

Photodiagnosis Photodyn Ther. 2016 Sep;15:53-8.

Photodynamic action of palmatine hydrochloride on colon adenocarcinoma HT-29 cells.[Pubmed: 27181460 ]

Palmatine hydrochloride (PaH) is a natural active compound from a traditional Chinese medicine (TCM). The present study aims to evaluate the effect of PaH as a new photosensitizer on colon adenocarcinoma HT-29 cells upon light irradiation.
METHODS AND RESULTS:
Firstly, the absorption and fluorescence spectra of PaH were measured using a UV-vis spectrophotometer and RF-1500PC spectrophotometer, respectively. Singlet oxygen ((1)O2) production of PaH was determined using 1, 3-diphenylisobenzofuran (DPBF). Dark toxicity of PaH was estimated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of PaH in HT-29 cells was detected at different time intervals. Subellular localization of PaH in HT-29 cells was observed using confocal laser fluorescence microscopy. For photodynamic treatment, HT-29 cells were incubated with PaH and then irradiated by visible light (470nm) from a LED light source. Photocytotoxicity was investigated 24h after photodynamic treatment using MTT assay. Cell apoptosis was observed 18h after photodynamic treatment using a flow cytometry with Annexin V/PI staining. Results showed that PaH has an absorption peak in the visible region from 400nm to 500nm and a fluorescence emission peak at 406nm with an excitation wavelength of 365nm. PaH was activated by the 470nm visible light from a LED light source to produce (1)O2. Dark toxicity showed that PaH alone treatment had no cytotoxicity to HT-29 cancer cells and NIH-3T3 normal cells after incubation for 24h. After incubation for 40min, the cellular uptake of PaH reached to the maximum and PaH was located in mitochondria. Photodynamic treatment of PaH demonstrated a significant photocytotoxicity on HT-29 cells. The rate of cell death increased significantly in a PaH concentration-dependent and light dose-dependent manner. Further evaluation revealed that the early and late apoptotic rate of HT-29 cells increased remarkably up to 21.54% and 5.39% after photodynamic treatment of PaH at the concentration of 5μM and energy density of 10.8J/cm(2).
CONCLUSIONS:
Our findings demonstrated that PaH as a naturally occurring photosensitizer has potential in photodynamic therapy on colon adenocarcinoma.

Luminescence. 2014 May;29(3):211-8.

Studies on the interaction of palmatine hydrochloride with bovine hemoglobin.[Pubmed: 23696111 ]

The interaction between bovine hemoglobin (BHb) and Palmatine hydrochloride (PMT) was investigated at different temperatures using multispectroscopy, as well as the effect of common metal ions (Ca(2+) , Mg(2+) , Zn(2+) , Cu(2+) , Fe(2+) , Fe(3+) , Co(2+) , Ni(2+) ) on the BHb-PMT system. Results showed that the quenching mechanism of PMT on BHb was a static process. The electrostatic force played an important role in the conjugation reaction between BHb and PMT. The order of magnitude of the binding constants (Ka ) was 10(4) , and the number of binding sites (n) in the binary system was ~ 1. The binding distance (r) was ~ 2.44 nm and the primary binding for PMT was located at β-37 tryptophan in the hydrophobic cavity of BHb. In addition, the Hill's coefficients were ~ 1. Synchronous and circular dichroism spectra revealed that the microenvironment and the conformation of BHb were changed during the binding reaction.