Pharmacodynamic interaction of 3α-hydroxymasticadienonic acid and diligustilide against indomethacin-induced gastric damage in rats.

The aims of the study were to evaluate the pharmacodynamic interaction between 3α-hydroxymasticadienonic acid and diligustilide (DLG), isolated from the plants Amphiptherygium adstringens and Ligusticum porteri, respectively, using the indomethacin-induced gastric injury model, as well as their individual gastroprotective efficacy in this model. Male Wistar rats were orally administered with 3α-hydroxymasticadienonic acid, DLG or the mixture of 3α-hydroxymasticadienonic acid-DLG (at a fixed-ratio combination of 1:1, 1:3, and 3:1). Thirty minutes later, the gastric damage was induced by a single oral dose of indomethacin (30 mg/kg). Three hours later, the gastric injury (mm2 ) was determined. 3α-hydroxymasticadienonic acid and DLG as individual compounds showed a gastroprotective effect against indomethacin-induced gastric damage (p < .05). The effective dose (ED50 ) values for each compound were 6.96 ± 1.25 mg/kg for 3α-hydroxymasticadienonic acid and 2.63 ± 0.37 mg/kg for DLG. The isobolographic analysis performed showed that the combination exhibited super-additive interaction as the experimental ED50 values (Zexp) were lower than theoretical additive dose values (Zadd; p < .05). Our results identify the super-additive (synergist) interaction between 3α-hydroxymasticadienonic acid and DLG and the gastric safety of both compounds in the indomethacin-induced gastric injury model, suggesting their potential in the future as a strategy to decrease the gastric damage associated to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Liguisticum wallichii inhibits renal carcinoma progression by downregulating UBE3A and through suppression of NF-κB signaling.

Renal carcinoma accounts for a fifth of the morbidity among malignant tumors in China. Ubiquitin-protein ligase E3A (UBE3A) plays an important role in the occurrence and development of gene mutation-induced diseases. This study was designed to investigate the mechanism of Liguistium wallichii in treating renal carcinoma. Hematoxylin and eosin staining was applied to detect the pathological changes in a rat renal carcinoma model. The experimental group received L. wallichii treatment at 100 mg/kg every 48 h for 4 weeks, while the control group only received normal saline. The proliferation index Ki67 was measured by immunohistochemistry. Primary renal carcinoma cells were isolated and UBE3A expression was measured by quantitative polymerase chain reaction. The related signaling pathway was screened by the Pathway Finder Array. pP65 nuclear import was detected by immunofluorescence. A total of 60 rats were used for the renal carcinoma model, of which 58 rats were successfully established and equally divided into two groups: L. wallichii and normal saline. Ki67 expression decreased in the L. wallichii group and was upregulated in the normal saline group. Histological analysis showed significant renal cell nucleus division in the normal saline group. The UBE3A level decreased after L. wallichii treatment compared to the level in the normal saline group. The Pathway Finder Array revealed that the NF-κB signaling pathway was activated, and pP65 presented obvious nuclear import in the normal saline group. In conclusion, L. wallichii inhibits renal carcinoma progression by downregulating UBE3A and suppressing the NF-κB signaling pathway.

Antinociceptive activity of Ligusticum porteri preparations and compounds.

CONTEXT: The roots and rhizomes of Ligusticum porteri Coulter & Rose (Apiaceae) are widely used in Mexican folk medicine for several purposes, including painful complaints. OBJECTIVE: The main goal of this work was to demonstrate the analgesic action in mice of some preparations and major compounds from L. porteri. MATERIALS AND METHODS: The extracts, aqueous (AE) and organic (OE), the essential oil (EO) and major compounds (10-316 mg/kg) from L. porteri were evaluated as potential antinociceptive agents using the acetic acid-induced writhing and hot plate tests in ICR mice. RESULTS: All preparations tested exhibited significant antinociceptive effect in the two animal pain models selected. AE and EO were more effective in the writhing test while OE had a better effect in the hot-plate model. On the other hand, Z-ligustilide (1) provoked an increment in the latency period to the thermal stimuli in the hot-plate test at a dose of 31.6 mg/kg, and a decrease in the number of abdominal writhes at 10 mg/kg. Z-3-butylidenephthalide (2) induced a dose-dependent antinociceptive action in the hot-plate assay; this compound was also effective for controlling the pain provoked by chemical irritation at the doses of 10 and 31.6 mg/kg. Finally, diligustilide (3) inhibited the number of writhing responses at all doses tested but was inactive in the hot-plate model. CONCLUSION: The present investigation provides in vivo evidence supporting the use of L. porteri to treat painful conditions in folk medicine.

Quantitative HPLC method for determining two of the major active phthalides from Ligusticum porteri roots.

Z-Ligustilide (1) and Z-6,6',7,3'-alpha-diligustilide (2), two of the major active phthalides of the medicinal plant Ligusticum porteri (osha), were chosen for the development and validation of an HPLC-diode array detection method suitable for QC of the crude drug. The method used gradient elution to achieve separation on a Hibar RT LiChrospher 100 C18 column. The LOD values were 29 and 45 microg/mL, and the LOQs were 89 and 125 microg/mL, respectively. The method showed good intraday precision (%RSD: 0.7 for 1 and 3.1 for 2) and interday precision (%RSD: 1.2 for 1 and 1.8 for 2). The method was used for the analysis of 1 and 2 in crude drug samples and several herbal preparations from Mexico and the United States. Quantitative analysis showed that the content of the two phthalides varied significantly among the samples. All the samples contained higher concentrations of 1 (0.15-2.5%) than 2 (0.002-1.0%). The profiles of volatile compounds in the essential oil obtained by hydrodistillation and solid-phase microextraction of L. porteri roots were analyzed by GC-MS. Thirty one chemical constituents (> 99.7% of the total content) were identified in the essential oil, which was characterized by the presence of a high percentage of phthalides (44.61%) and sesquiterpenes (10.69%). The major light volatile components extracted by solid-phase microextraction were monoterpenes.

Chronic toxicity, genotoxic assay, and phytochemical analysis of four traditional medicinal plants.

Four medicinal plants--Tecoma stans, Ligusticum porteri, Monarda austromontana, and Poliomintha longiflora, which are distributed in tropical and subtropical countries of the American continent--are widely used in folk medicine to treat diseases such as diarrhea and dysentery. In addition, T. stans and P. longiflora are extensively used as hypoglycemic agents, and M. austromontana and P. longiflora are used as condiments. The plants were collected, identified, dried, and pulverized. Solvent extraction was prepared by maceration of the plant samples, and the phytochemical composition of the extracts was determined by using standard analysis procedures. Phytochemical analysis showed the presence of triterpenoids/steroids, flavonoids, and phenols/tannins and, in L. porteri, traces of alkaloids. After the elimination of solvents in vacuo, the extracts were administrated to Drosophila larvae to test their toxicity and genotoxicity. Third instar larvae were chronically fed with the phytoextracts. The extract from L. porteri was toxic, whereas those from T. stans, P. longiflora, and M. austromontana were not. Genotoxic activities of the 4 plants were investigated by using the wing-spot assay of D. melanogaster. Mitomycin C was used as a positive control. No statistically significant increase was observed between treated sample series and a concurrent negative (water) or solvent control sample series.

(Z)-3-butylidenephthalide from Ligusticum porteri , an α-glucosidase inhibitor.

An extract from the roots of Ligusticum porteri, orally administered to groups of normal and diabetic mice, showed significant hypoglycemic and antihyperglycemic effects. Experimental type-II DM was achieved by treating mice with streptozotocin 15 min after an injection of ß-nicotinamide adenine dinucleotide. (Z)-6,6',7,3'α-diligustilide (1), (Z)-ligustilide (2), 3-(Z)-butylidenephthalide (3), myristicin (4), and ferulic acid (5) were isolated from the active extract. When tested In Vivo, compounds 1-3 showed antihyperglycemic activity, with 3 being the most active. Compound 3 (56.2 mg/kg) decreased blood glucose levels in NAD-STZ-diabetic mice after an oral sucrose load, suggesting that its antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level. Furthermore, 3 inhibited the activity of yeast-α-glucosidase (IC(50) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM. Docking analysis predicted that 3 binds to the enzyme in a pocket close to the catalytic site, but different from that for acarbose, with a K(i) of 11.48 mM. Compounds 1 and 2 did not affect α-glucosidase In Vivo, but altered glucose absorption by a mechanism yet to be determined. The stimulatory effect of 5 on insulin secretion, present in high amounts in the extract, has been demonstrated in previous investigations. The present study provides scientific support of the use of L. porteri in Mexican folk medicine for the treatment of diabetes.