Chemical constituents of Patrinia heterophylla Bunge and selective cytotoxicity against six human tumor cells

J Ethnopharmacol. 2019 May 23:236:129-135. doi: 10.1016/j.jep.2019.03.005. Epub 2019 Mar 7.

Abstract

Ethnopharmacological relevance: Patrinia heterophylla Bunge, known as "Mu-Tou-Hui" in China, is distributed in most provinces and regions of China. As a traditional medicinal plant, which was first found in <Ben- Cao-Gang- Mu>. In many traditional herbal books, there are records of "Mu-Tou-Hui" of treatment for uterine bleeding, cancer, swelling pain, leukemia, etc. However, there are few studies on the chemical constituents of Patrinia heterophylla Bunge.

Aim of the study: To investigate the chemical constituents of P. heterophylla and the basis of their antitumor activity.

Materials and methods: 15 compounds were isolated from roots and rhizomes of P. heterophylla by repeating various column chromatography techniques, whose structures were determined by organic spectrum analysis methods and compared with published data. The cytotoxicities were evaluated by MTT assay on six cancer cell lines: human melanoma cell (A375), human hepatocellular carcinoma cell (SMMC-7721), human gastric cancer cell (SGC-7901), human cervical cancer cell (HeLa), human colon cancer cell (HCT-116), and human breast cancer cell (MDA-MB-231). The apoptosis-inducing activities of compounds 1, 5, 12 and 15 in A375 tumor cell determined by flow cytometry.

Result: Five phenylpropanoids, ethyl caffeate (1), coniferaldehyde (5), trans-p-coumaryl aldehyde (6), caffeic acid methyl ester (12), and 3,4-dihydroxycinnamic acid (15), four acetophenones, 1-(2,4-dihydroxyphenyl) ethanone (2), 2',5'-Dihydroxyacetophenone (3), cynanchone A (8), and cynandione A (10), two phenols, vanillin (4) and catechol (9), two iridoids, sarracenin (7) and patriscabrol (11), one alkane, tetracosane (14), and one coumarin, scopoletin (13), were isolated from the EtOH extracts. Of them, compounds 1-10, 12 and 14-15 were isolated for the first time from the roots of P. heterophylla. Compounds 1 and 15 were reported for the first time with in vitro inhibitory activity against tumor cells. MTT assay showed that compounds 1, 5-9, 12-13 and 15 had selective cytotoxic activities (IC50 27.20-163.03 μM) against tumor cells. Apoptosis detected by flow cytometry revealed that compounds 1, 5, 12 and 15 can induce apoptosis for A375 at low concentrations when the concentrations of compounds 1, 5, 12 and 15 are the value of 14, 40, 34, 108 μM, the percentages of apoptotic cells were about 50%.

Conclusions: Compounds 1-10, 12 and 14-15 were isolated for the first time from the P. heterophylla. This result enriches the previous studies on the chemical constituents of P. heterophylla. Compounds 1 and 15 were reported for the first time to have cytotoxic activities against tumor cells. Compounds 1, 5, 6, 7, 12, 15 showed cytotoxic activities against tumor cells. This result reveals that the active ingredient of P. heterophylla are composed of phenylpropanoids, iridoids and coumarins. This study provides some theoretical basis for the anti-tumor research of P. heterophylla.

Keywords: 1-(2,4-dihydroxyphenyl) ethanone (PubChem CID: 6990); 2′,5′-Dihydroxyacetophenone (PubChem CID: 10279); 3,4-Dihydroxycinnamic acid (PubChem CID: 689043); Caffeic acid methyl ester (PubChem CID: 689075); Catechol (PubChem CID: 289); Chemical constituents; Coniferaldehyde (PubChem CID: 5280536); Cynanchone A (PubChem CID: 101687172); Cynandione A (PubChem CID: 10063465); Cytotoxicity; Ethyl caffeate (PubChem CID: 5317238); Patrinia heterophylla Bunge; Patriscabrol (PubChem CID: 11074397); Sarracenin (PubChem CID: 427877); Scopoletin (PubChem CID: 5280460); Tetracosane (PubChem CID: 12592); Trans-p-coumaryl aldehyde (PubChem CID: 641301); Vanillin (PubChem CID: 1183); apoptosis.

MeSH terms

  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Patrinia / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry*
  • Rhizome / chemistry

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts