Antitumor chemical constituents of Toddalia asiatica (Linn) Lam root bark and its rational alternative medicinal parts by multivariate statistical analysis

Abstract

<jats:title>Abstract</jats:title> <jats:p> <jats:italic>Toddalia asiatica</jats:italic> (Linn) Lam (<jats:italic>T. asiatica</jats:italic>) as a traditional Miao medicine was investigated to find rational alternative medicinal parts for <jats:italic>T. asiatica</jats:italic> root bark and its antitumor chemical constituents by quantitative pharmacognostic microscopy, high performance liquid chromatography (HPLC) fingerprint and multivariate statistical analysis. A bivariate correlation analysis method based on microscopic characteristics and content of chemical constituents was established for the first time, there were some regular discoveries between powder microscopic characteristics and common chromatographic peaks of <jats:italic>T. asiatica</jats:italic> through quantitative pharmacognostic microscopy, cork cells, calcium oxalate square crystal, brown clump, starch granule and phloem fiber, as powder microscopic characteristics may be placed where the main chemical constitutes were enriched. Scores plot of principal component analysis (PCA) and dendrogram of hierarchical clustering analysis (HCA) showed that 18 <jats:italic>T. asiatica</jats:italic> samples were distinguished correctly, clustered clearly into two main groups as follows: S01∼S03 (root bark) and S07∼S09 (stem bark) in cluster 1, S04∼S06 and S10∼S18 in cluster 2. Nineteen common peaks were obtained in HPLC fingerprint of <jats:italic>T. asiatica</jats:italic>, loadings plot of PCA indicated seven compounds played important roles in different part of samples (P10 &gt; P08 &gt; P07 &gt; P14 &gt; P16 &gt; P17 &gt; P19), peaks 04, 06, 07, 08, 10 were identified as hesperidin, 4-methoxycinnamic acid, toddalolactone, isopimpinlline and pimpinellin. MTT assay was used to determine the inhibitory activity of different medicinal parts of <jats:italic>T. asiatica</jats:italic> on human breast cancer MCF-7 cells, all parts of <jats:italic>T. asiatica</jats:italic> had different inhibitory effects on MCF-7 cell lines, root and stem barks of <jats:italic>T. asiatica</jats:italic> showed the best inhibitory activity. The relationship between chemical constituents and the inhibitions on MCF-7 cell had been established, significant antitumor constituents of <jats:italic>T. asiatica</jats:italic> were identified by correlation analysis, the order of the antitumor effect of the main compounds was P07 (toddalolactone) &gt; P16 &gt; P06 (4-methoxycinnamic acid), P11 &gt; P18 &gt; P10 (pimpinellin) &gt; P08 (isopimpinellin) &gt; P01 &gt; P19 &gt; P14 &gt; P04 (hesperidin) &gt; P17, which were antitumor chemical constituents of <jats:italic>T. asiatica</jats:italic> root bark. <jats:italic>T. asiatica</jats:italic> stem bark was the most rational alternative medicinal part for <jats:italic>T. asiatica</jats:italic> root bark.</jats:p>

Comprehensive study of secondary metabolite profile and pharmacological effects of medicinal plant Toddalia asiatica

“…Bivariate analysis was used to establish a relationship between nineteen distinct peaks and the anti-tumor inhibition rate of different T. asiatica medicinal components, which was reflected in the form of peak correlation coefficients. Statistical investigations revealed that various compounds in T. asiatica exhibited anticancer activities, including toddalolactone, 4-methoxycinnamic acid, pimpinellin, isopimpinellin, and hesperidin appearing in that order (Luo et al, 2021).…”

“…Animal model experiments conducted in proving the hemostatic action of compounds isolated from the root bark of the plant T. asiatica was available in the literature, the considerable number of natural compounds such as furocoumarins isolated from T. asiatica plant root bark had been studied successfully by the considerable number of researchers (Luo et al, 2021;Ma et al, 2021). However, there is no scientific document available on comparative studies on pharmacologically active molecules that were isolated from the different active parts of the plant T. asiatica.…”

CF–PK–PD analysis of natural hemostatic compounds from Toddalia asiatica (Linn) Lam root bark in rats

“…In addition to having anti-bacterial, anti-oxidant activities and other conventional pharmacological actions [1,2], hemostasis was its most significant pharmacological effect, had been applied and validated in thousands of years of Chinese folk history, which also led to derive its Chinese name Feilong Zhangxue or Jianxuefei [3][4][5]. Our research group earlier found the anti-inflammatory, analgesic, hemostatic and anti-tumor effects of T. asiatica which were experimentally verified [6][7][8], a large number of characteristic compounds including coumarins, alkaloids and flavonoids were isolated from ethyl acetate (EA) part, n-butanol (n-B) part in T. asiatica root bark which were also presumably deduced by high resolution mass spectrometry and chemical databases [9][10][11][12], most of these compounds were coumarins, more specifically furan coumarin. T. asiatica as a kind of natural medicines, it itself couldn't escape the congenital deficiency of these drugs which were rich in a variety of natural chemical compounds, diverse and complex pharmacological mechanisms to ultimately achieve the same therapeutical effect.…”