Ethnopharmacology, Phytochemistry, and Pharmacology of the Genus Glehnia: A Systematic Review
Table 3
Pharmacological activities of various bioactive ingredients in G. littoralis.
Pharmacological activity
Bioactive ingredient
Methods
Results and pathway
References
Immunoregulatory activity
Polysaccharide of Radix G. littoralis. (GLP)
The model of yin deficiency in mice was constructed with thyroxine and reserpine. High-dose group of GLP (800 mg·(kg·d)−1), medium-dose group of GLP (600 mg·(kg·d)−1), and low-dose group of GLP (400 mg·(kg·d)−1) are given by gavage for 6 consecutive days.
GLP obviously increased the weight of yin deficiency mice and also significantly raised the levels of antibody-forming cells in interperitoneal cavity ( or ), and enhanced delayed-type hypersensitivity (DTH) reaction in mice (), but it had no effect on peritoneal macrophage coefficient and index.
Using cyclophosphamide to establish immunosuppressed mice model and the effects of the SFE extraction on it were studied. For 6 consecutive days, the intraperitoneal injection dose was 4 or 2g·kg−1·d−1 dissolved by DMSO with Glehniae SFE-CO2 extract.
The SFE extraction restored part of the immunological function in immunosuppressed mice. CD3+ T, CD3+ CD4+ T, and CD3+ CD8+ T in the low-dose group and the high-dose group were all higher than the immunity inhibition group, but lower than the normal control group ().
Using cyclophosphamide to establish immunosuppressed mice model. For 10 consecutive days, the intraperitoneal injection dose was 4, 2, or 1 g·kg−1 with the root of G. littoralis.
G. littoralis can increase the weight of thymus gland and spleen, enhance the ability of mouse peritoneal macrophages to engulf neutral red, and improve the tumor killing rate of mouse lymphocytes and the killing ability of natural killer cells.
The mouse spleen lymphocytes were treated with 250, 125, 62.5, 31.25, 15.63, 7.8 mg·L−1 polysaccharide in the root of G. littoralis, and the three fractions (GRP-1, GRP-2, and GRP-3) were determined by MTT assay.
In vitro immunological activity results showed that the three polysaccharide components exhibited good immune activity.
The drug extracts from leaves and stems of G. littoralis were administered to the mice continuously for 15 days, and the intraperitoneal injection dose was 2.34 g·kg−1 or 0.59 g·kg−1. After 15 days, hemolytic value of mice was discussed.
Mice were given different doses of extracts from leaves and stems of G. littoralis. After 15 days compared with the control group, hemolytic value of mice in the water extract 2.34 g·kg−1 dose group, the alcohol extract 2.34 g·kg−1 dose group, and the American ginseng capsule group were significantly increased (). Extracts from leaves and stems of G. littoralis can regulate humoral immunity.
Crude extract and solvent-partitioned fraction of G. littoralis
Crude extract and solvent-partitioned fraction of G. littoralis were against human gastric cancer (AGS), HT1080 and U937 human cancer cells. The cells were treated with 5, 10, and 50 μg·mL−1.
The crude extracts and solvent fractions dose-dependently inhibited cell proliferation. Especially, n-hexane and 85% aqueous MeOH fractions exhibited comparatively higher antiproliferative effects and reduced expressions of Bcl-2, COX-2, and iNOS genes.
To investigate the anticancer activity of polysaccharide (PGL) from G. littoralis on human lung cancer cell line A549, after incubation, the cells were treated with various concentrations (380, 260, 160, 80, 40, and 20 μg·mL−1) of PGL.
PGL could significantly reduce A549 cell proliferation in a time- and dose-dependent manner. In addition, PGL displayed an inhibitory activity for the A549 cells migration in Transwell migration assay. The results from both flow cytometry analysis and Hochst 3342 staining of apoptotic cells indicated that PGL could promote apoptosis and induce cycle arrest of A549 cells.
The G. littoralis crude drug slices were treated to human bronchial cell line16HBE and human lung cancer cell line H460 with 15 mg·mL−1, 10 mg·mL−1, and 5 mg·mL−1.
The extracts of G. littoralis from 5 mg·mL−1 to 15 mg·mL−1 had no toxic effect on 16HBE cells, significantly inhibited the proliferation and invasion ability of H460 cells, and upregulated the expression and secretion of TIMP2 in H460 cells. G. littoralis can upregulate the expression and secretion of TIMP2 in lung cancer cells and thus inhibit its migration and invasion.
Purification of the n-hexane-soluble fraction of the whole plant of G. littoralis led to the isolation. All isolated compounds of G. littoralis from 0.5 to 50 μM were evaluated by monitoring the inhibition of NO production in LPS-stimulated murine macrophage RAW 264.7 cells with aminoguanidine as the positive control (IC50 value: 16.6 μM).
Extract of the whole plants of G.littoralis exhibited the significant inhibitory activity of the NO production with IC50 values ranging from 7.4 μM to 44.3 μM.
Human hepatoma cell line HepG2 cells were treated to GLEA (50, 100, and 200 μg·mL−1). Cell viability was evaluated by the MTT method. AST, ALT, and LDH production in a culture medium and intracellular MDA, GSH, and SOD levels were determined.
G. littoralis ethyl acetate extract significantly increased the relative cell viability by 7.11, 9.87, and 14.39%, respectively, and reduced the level of ALT by 10.39%, 34.27%, and 52.14%, AST by 9.89%, 15.16%, and 32.84%, as well as LDH by 15.86%, 22.98%, and 24.32% in culture medium, respectively. G. littoralis ethyl acetate extract could also remarkably decrease the level of MDA and increase the content of GSH and SOD in the HepG2 cells.
Prolyl oligopeptidase (POP) (50 μl, 0.1 U·mL−1), Tris-HCl buffer (pH7.0, 840 μl), and sample solution (10 μL) saved 5 min at 30°C. Add 2 mmol·L−1 Z-G ly-Pro-pNA 100 μl solution of 40%, 1-4-dioxide-hexacyclic ring, mix well, store 30 min, absorption was measured at 410 nm.
The inhibition rate of ethyl acetate extraction was 50%, which was similar to that of 1 mmol·L−1 proprolinal, the positive control, showing certain antipop enzyme effect.
The ethyl acetate fraction of the G. littoralis extract
The acetic acid-induced writhing test and the pentobarbital-induced hypnosis method were used to test for the analgesic effect at an oral dose of 1 g·kg−1.
The ethyl acetate fraction induced significant analgesia at an oral dose of 1 g·kg−1 and potently prolonged the sleeping time (>400% at 1 g·kg−1).
To investigate the effects of G. littoralis root hot water extract on 3T3-L1 cell adipogenesis at dose of 400 μg·mL−1, 200 μg·mL−1, 100 μg·mL−1, 50 μg·mL−1 and in high-fat diet- (HFD-) induced obese mice. We measured intracellular lipid accumulation using oil red O staining in vitro. We also determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice.
The G. littoralis root hot water extract dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. The GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo.
Petroleum ether extract of the root of G. littoralis
To study the inhibitory effect of the root of G. littoralis petroleum ether part on TGF-β1-induced epithelial-mesenchymal transition in non-small-cell lung cancer A549, tested RT-qPCR at dose of 150 mg·L−1, 100 mg·L−1, and 50 mg·L−1.
The petroleum ether extract of Glehniae Radix could inhibit the growth of A549 cells in a concentration-dependent manner. The root of G. littoralis petroleum ether part group could effectively inhibit mRNA expressions of Col I, Vimentin, and α-SMA, but improve the expression of E-cadherin.
The water-soluble portion of G. littoralis (petroleum ethyl acetate fraction)
The antigastric ulcer activity of H20-soluble fraction was evaluated using the HCl/EtOH-induced gastric ulcer in mice. Then the water-soluble portion of G. littoralis from ethyl acetate fraction and petroleum of ethanol extract inject dose was 400 mg·mL−1 or 200 mg·mL−1, and the hydroxyl radical scavenging activity of H2O-soluble fraction was examined.
The results showed that the ulcer inhibition rate of the water-soluble part groups and the positive control group was 6.4%, 38.5%, and 60.8%, showing a certain antiulcer effect.
