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REVIEW ARTICLE
Year : 2023 | Volume
: 9
| Issue : 3 | Page : 243-257
Research progress on Rodgersia and predictive analysis on its quality markers
Ling-Ling Chu1, Bin Li1, Jia Wu1, Ling Jiang1, Xu-Dong Zhou1, Wen-Bing Sheng1, Cai-Yun Peng1, Salman Zafar2, Ping-An Liu3, Wei Wang1
1 TCM and Ethnomedicine Innovation and Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China
2 Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan
3 TCM and Ethnomedicine Innovation and Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine; Hunan Academy of Chinese Medicine, Changsha, Hunan, China
Correspondence Address:
Prof. Bin Li
TCM and Ethnomedicine Innovation and Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan
China
Dr. Ping-An Liu
TCM and Ethnomedicine Innovation and Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, Hunan; Hunan Academy of Chinese Medicine, Changsha 410208, Hunan
China
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.343650
Rodgersia is a traditional Chinese medicine that contains a variety of chemical constituents, including flavonoids, terpenoids, phenylpropanoids, gallic acid derivatives, steroids, volatile oils, and tannins, with anti-inflammatory, antioxidant, antitumor, antibacterial, antivirus, hepatoprotective, and other properties. In this paper, the main chemical constituents and pharmacological effects of Rodgersia are summarized. On this basis, the quality markers of this genus were predicted based on chemical composition, traditional medicinal properties, traditional efficacy, and measurable components. This review provides the basis for in-depth research, utilization, and quality control of Rodgersia.
Keywords: Bergenin, chemical constituents, pharmacological activity, quality marker, Rodgersia
The Rodgersia genus belongs to the Saxifragaceae family, which contains five species and three variations, and is distributed in East Asia and the Himalayas. There are four species and three varieties of this genus in China, which are Rodgersia podophylla, Rodgersia aesculifolia, Rodgersia aesculifolia var. strigosa, Rodgersia pinnata, Rodgersia pinnata var. strigosa, Rodgersia sambucifolia, and Rodgersia sambucifolia var. strigosa. Except for R. podophylla and R. aesculifolia var. strigosa, the species are unique to China and are distributed in the northeast, northwest, north, central, and southwest of China.[1] Modern pharmacological studies have shown that the chemical constituents of Rodgersia have antimalarial, antiviral, antioxidant, anti-inflammatory, and antibacterial activities. To improve the use and development of Rodgersia, this article systematically reviews the chemical components and pharmacological effects of Rodgersia and predicts and analyzes its quality markers (Q-Markers).
There are many confusing aliases for each species of Rodgersia. In previous studies, R. aesculifolia was named “Guidengqing” (different homophonic words in Chinese);[2],[3],[4] thus, we have summarized the aliases of each species in [Table 1]. The literature cited in the article was mainly queried using databases, such as SciFinder, CNKI, and PubMed. The search terms were Rodgersia, Guidengqing, and the Chinese name for this genus.
Chemical ConstituentsThe earliest research on the chemical constituents of Rodgersia can be traced back to the 1970s. For the first time, The Institute of Soil and Water Conservation studied the composition of R. aesculifolia. In a later study, 104 compounds were isolated from this genus, including flavonoids, terpenoids, phenylpropanoids, gallic acid derivatives, steroids, and volatile oils. In addition, starch, sugar, tannins, and many glycosides are also present in this genus.
Flavonoids
Flavonoids are one among the main components of Rodgersia and have extensive pharmacological activities. At present, 27 flavonoids (1–27) have been isolated from Rodgersia, including flavonols, flavan-3-ol, flavones, and dihydrochalcones. The sources of the flavonoids are shown in [Table 2], and their structures are shown in [Figure 1].
Terpenoids
Currently, 22 terpenes and their derivatives (28–49) have been reported in Rodgersia, including monoterpenes, diterpenes, and triterpenes. The sources of the terpenes are shown in [Table 3], and their structures are shown in [Figure 2].
Phenylpropanoids
To date, 17 phenylpropanoids (50–66) have been isolated from this genus, including simple phenylpropanoids, lignans, and coumarins. The sources of the phenylpropanoids are shown in [Table 4], and their structures are shown in [Figure 3].
Figure 3: Structures of phenylpropanoids isolated from the genus RodgersiaGallic acid derivatives
There are several gallic acid derivatives in Rodgersia, and gallic acid derivatives are important components of this genus since they exert medicinal effects. At present, 18 gallic acid derivatives (67–84) have been isolated from this genus. The sources of gallic acid derivatives are shown in [Table 5], and their structures are shown in [Figure 4].
Figure 4: Structures of gallic acid and its derivatives isolated from the genus RodgersiaSteroids
To date, six steroids (85–90) have been isolated from Rodgersia. [Table 6] shows their plant sources, and [Figure 5] shows their structures.
Organic acid and other compounds
In addition to these components, there are 16 organic acids and other compounds (91–106) in Rodgersia. [Table 7] shows their plant sources, and [Figure 6] shows their structures.
Figure 6: Structures of organic acids and other compounds isolated from the genus Rodgersia Pharmacological Activities Anti-inflammatory activity
Rodgersia plants exhibit good anti-inflammatory effects. In a clinical research on rheumatoid arthritis, Yu et al. found that R. aesculifolia granules (Suogudan granules) could relieve joint pain and swelling and reduce the period of morning stiffness, the time required for a 15-minute walk, the onset and duration of analgesia, the onset of swelling, and the erythrocyte sedimentation rate, rheumatoid factor, and antistreptolysin O conversion in rats. There were no obvious adverse reactions during the treatment of rheumatoid arthritis.[23] Rodgersinol (53), isolated from the aerial part of R. podophylla, could inhibit nitric oxide synthase and cyclooxygenase, thereby inhibiting the occurrence of inflammation in the body.[22] Wang et al.[24],[25] found that the water, total anthraquinone, and tannin extracts of R. aesculifolia could inhibit the inflammatory reaction by inhibiting the production and release of cytokines (IL-6, IL-1 β, and TNF-α). However, bergenin (75) only had an inhibitory effect on IL-6, and its anti-inflammatory effect was slightly lower than that of the aqueous extract of R. aesculifolia. The research showed that the extract of R. podophylla leaves might have anti-inflammatory effects on RAW264.7 cells by activating HO-1, ROS, GSK3 β, p38, and Nrf2 signals and inhibiting NF-κB and MAPK signals.[26]
Hepatoprotective effects
The chemical constituents of the genus Rodgersia have a certain hepatoprotective effect; however, there are few studies in this area at present. Chin et al.[6] found that kaempferol-3-O-α-L-rhamnopyranoside (6), quercetin-3-O-α-L-rhamnopyranoside (10), quercetin-3-O-a-L-(5''-O-acetyl)-arabinofuranoside (11), and quercetin-3-O-α-L-(3''-O-acetyl)-arabinofuranoside (13) isolated from R. podophylla have hepatoprotective effects in primary cultures of rat hepatocytes injured by H2O2. Bergenin (75), found in the genus Rodgersia, has also been shown to have a hepatoprotective effect.[27],[28],[29]
Antibacterial activity
Studies have found that plants of the genus Rodgersia show broad-spectrum antibacterial effects and have inhibitory effects on Streptococcus pneumoniae, Bordetella bronchis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae.[30],[31] Han et al. found that an acetone extract of R. aesculifolia had a strong inhibitory effect on Gibberella zeae, Exserohilum turcicurn, and Phytophthora capsici leaonian, with inhibition rates of 68.31%, 100%, and 88.76%, respectively.[32]
Biological toxicity
Zhang[33] conducted an acute toxicity test on ethyl acetate and acetone extracts of R. aesculifolia in mice, and their experimental results showed that R. aesculifolia was nontoxic. The acute and subacute toxicity of the acetone extract of R. aesculifolia on mice and rats was studied, and the results showed that the acetone extract did not affect body weight, dietary desire, physiological blood indexes, liver function, and organs of rats, such as the heart, liver, spleen, lung, and kidney.
Mycoplasma inhibition
Research has shown that the acetone extract of R. aesculifolia has an inhibitory effect on Mycoplasma, particularly the n-butanol and ethyl acetate fractions.[33]
Antiviral activity
Xu et al.[34] studied four different polar parts of an ethanol extract of R. aesculifolia to suppress viruses. The results showed that the ethanol extract of R. aesculifolia had a broad-spectrum antiviral effect, but the water decoction of R. aesculifolia had no antiviral activity. Relevant studies have shown that bergenin (75) in the genus Rodgersia has anti-HIV effects.[35]
Antioxidant activity
Wang et al.[36] found that the chelating ability of R. aesculifolia to Fe2+ increased with increasing concentration. When the ethanol extract of R. aesculifolia was 1.8 mg·mL−1, the chelation rate reached 75%. The inhibitory rate of xanthine oxidase reached its highest at 85.18% when the concentration of the ethanol extract of R. aesculifolia was 1.25 mg·mL−1. Studies have shown that the highest clearance rate of the total phenolic extract of R. aesculifolia on DPPH was equivalent to that of the reference butyl hydroxyanisole (BHA), reaching 98.03%, and its IC50 value was lower than that of BHA.[37] It has been found that the antioxidant capacity of the total polyphenol extract and components of R. aesculifolia was very close to that of Vc.[38],[39] The autoxidation method was used to test the scavenging effect of the superoxide radicals of tannins and anthraquinone extracts from R. aesculifolia. When the concentration of tannin and anthraquinone extracts was 3 mg·mL−1, the clearance rate was the highest at 86.1% and 91.7%, respectively.[40] It has been reported that the flavonoids of R. aesculifolia have a scavenging effect on hydroxyl radicals, nitrite, and superoxide anions.[41] The antioxidant effects of the genus Rodgersia are closely related to its polyphenols; therefore, Rodgersia can be used as a natural antioxidant.
Antitumor activity
The compounds isolated from R. pinnata, such as (E)-3,7-dimethyl-1-O-[α-L-arabinofuranosyl-(1 → 6)-β-D-glucopyranosyl] -oct-2-en-7-ol (36), 3α-O-(E)-p-hydroxy-cinnamoyl-olean-12-en-27 oic acid (49), and bergenin (75), have inhibitory effects on human gastric adenocarcinoma cell beads BGC-6823, with IC50 values of 5.85, 9.12, and 6.97 μg·mL−1, respectively, and 3 β-hydroxy-olean-12-en-27-oic acid (47) has inhibitory effects on the prostate cancer cell line DU-145, with an IC50 of 8.08 μg·mL−1.[9] Studies have shown that the ethyl acetate extract of R. aesculifolia has an inhibitory effect on MCF-7 breast cancer cells. The ethyl acetate and ethanol extracts of R. aesculifolia can inhibit the growth of gastric cancer cells by inhibiting the expression of the antiapoptotic protein Bcl-2 and enhancing the expression of the proapoptotic protein Bax, which can also reduce the production of the arachidonic acid metabolite Prostaglandin E2 (PGE2), which may be one of its mechanisms to inhibit gastric cancer cells.[40],[42]
Antimalarial activity
Bergenin isolated from R. aesculifolia has an inhibitory effect on Plasmodium falciparum at a concentration range of 0.1–50 μg·mL−1. At a dose of 50 μg·mL−1, it completely inhibited the growth of P. falciparum and had no cytotoxicity to normal red blood cells and mammalian cells. The antimalarial effect of bergenin in vivo is weaker than that in vitro.[43]
Immunomodulatory effects
Bergenin, a compound that exists abundantly in the genus Rodgersia,[44],[45] has immunomodulatory effects.[46],[47] Gao et al. found that the complex of R. pinnata polysaccharide and Erigeron breviscapus flavone can stimulate the production of white blood cells and lymphocytes and increase immunoglobulin (Ig) G levels, thereby enhancing immunity.[48] The flavonoids of R. pinnata can promote the proliferation of red blood cells, white blood cells, neutrophils, and lymphocytes and increase serum IgG and IgM concentrations in rats, indicating that the flavonoids of R. pinnata can enhance humoral immunity in the body.[49]
Other activities
A preliminary clinical study of R. aesculifolia found that it has an effect on dysentery, diarrhea, uterine prolapse, hemorrhoids, and chronic bronchitis.[4] The R. aesculifolia mixture has been reported to have a therapeutic effect on bacillary dysentery, with a short course of treatment and a high curative effect.[50] Feng et al. studied the effects of R. aesculifolia bioadhesive tablets on cyclophosphamide-induced immunocompromised mice and found that the bioadhesive tablets could protect the thymus and spleen and enhance the clearance of foreign bodies.[51]
The pharmacological activities of monomeric compounds and extracts of the genus Rodgersia are summarized in [Table 8].
Table 8: Pharmacological effects of monomeric compounds or plant extracts in genus Rodgersia Quality Marker Prediction of Rodgersia Chemical compositions are the material basis of traditional Chinese medicine (TCM) that prevent and cure diseases, and pharmacopoeia quality monographs are chemical marker based, which ensures consistency in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. The intrinsic “multicomponent and multitarget” feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of Western medicine. Liu[52],[53] first proposed a new concept of Q-Marker for TCM; the Q-Marker of TCM refers to the intrinsic or processing/preparation-resultant chemical substances that are closely associated with the functional properties that exist in the raw materials and products of TCM (involving decoction pieces, decoctions, extractives, and Chinese patent medicines), which can be used as indicators for quality control of TCM to embody safety and effectiveness. In contrast to conventional chemical markers, Q-Markers are specific, effect-related, and aligned with the basic theory of TCM (nature/flavor and channel entry and the formulation principle). Therefore, Q-Marker-based TCM quality control is considered to be more scientific. Rodgersia is a multisource plant with complex components, rich resources, and wide distribution. Based on the summary of the chemical constituents and pharmacological effects of the genus Rodgersia, this article makes a Q-Marker prediction for Rodgersia to provide a scientific basis for the establishment and improvement of the quality control standards of Rodgersia.
Quality marker prediction analysis based on original plant genetics and chemical composition characteristics
The genus Rodgersia belongs to the Saxifragaceae family and is mainly distributed in North Korea, Japan, Nepal, Sikkim, India,[1] and many places in China. There are five species and three varieties of this genus and four species and three varieties in China. The morphology of the species and varieties of Rodgersia are relatively similar and not easy to distinguish. Li et al.[54],[55] studied and analyzed the phenotype, geographical distribution, habitat, and reserves of this genus. This study provides a basis for distinguishing between different species of the genus. Rodgersia contains many kinds of chemical constituents, including volatile oils, flavonoids, terpenes, phenylpropanoids, gallic acid derivatives, steroids, and tannins. Among them, gallic acid derivatives, flavonoids, and tannins are the main components of Rodgersia,[24],[25],[40] which is also the material basis for its efficacy.
Bergenin is abundantly present in plants of the genus Rodgersia. Chen et al.[44] used the high-performance liquid chromatography (HPLC) method to compare the content of bergenin in plants of the genus Rodgersia and found that the average content of bergenin in R. sambucifolia was 5.59%, followed by var. strigosa, with an average bergenin content of 4.51%.[48] The bergenin content was relatively low in R. pinnata.
Research has also shown that gallic acid derivatives are the main secondary metabolites of plants of the Rodgersia genus and their effective components. According to the chemical composition summary above and related literature analysis, gallic acid is the precursor of gallic acid derivatives. Gallic acid undergoes methylation, esterification, and glycosylation by a series of enzymes to form various derivatives. Among these, bergenin and its derivatives are the main derivatives of gallic acid. Masatoshi and Seiichi[56],[57] proved that bergenin is formed by the formation of C-glycosides from gallic acid and glucose, followed by cyclization and methylation. Bergenin is further methylated, glycosylated, and esterified to form various derivatives. The possible biosynthetic pathways of the characteristic gallic acid derivatives in Rodgersia are shown in [Figure 7]. By distinguishing the taxonomic characteristics of Rodgersia, studying genetic relationships, and analyzing and summarizing the composition characteristics, gallic acid and bergenin can be used as Q-markers of Rodgersia [Figure 7].
Figure 7: Possible biosynthesis pathways of characteristic gallic acid derivatives in Rodgersia. *Compounds 67 and 75 can be used as the main selection objects for quality markersQuality marker prediction analysis based on traditional medicinal properties
The theory of TCM properties is the core content of TCM theory, and it is an important theoretical basis for guiding the clinical use of TCM. Therefore, it should also be used as a base for Q-Marker prediction of the genus Rodgersia. Rodgersia is astringent, bitter, slightly sweet, and mid-natured.[45] Zang[58] found that the chemical components of astringent medicines are mainly tannins; those of bitter medicines are mainly saponins and alkaloids; and those of sweet medicines are mainly saponins, amino acids, and carbohydrates. In addition, Xin et al. and Chen et al.[59],[60] found that the flavonoid and sugar contents in mid-natured TCM were the highest. According to the above analysis, it can be considered that tannins, flavonoids, sugars, and saponins are the material basis of the “properties” of the genus Rodgersia, which can be used as the main choices of Q-Markers.
Quality marker prediction analysis based on traditional efficacy
The efficacy of TCM is a summary and generalization of the clinical therapeutic effects under the guidance of TCM theory. This is an important theory guiding the clinical use of TCM. According to the definition and requirements of Q-Markers, traditional efficacy can be used as an important basis for the prediction of Q-Markers in the genus Rodgersia. Rodgersia has the functions of clearing heat and detoxification, hemostasis, antidiarrhea, dispelling wind, and astringency and treating traumatic bleeding, turbidity, sore throat, uterine prolapse dysentery, irregular menstruation, and chronic diarrhea.[61] Modern pharmacological studies have shown that the genus Rodgersia has antitumor, antimalarial, and anti-inflammatory effects. Studies have found that the antibacterial, anti-inflammatory, and antiviral pharmacological effects of plants of the genus Rodgersia have the effect of “clearing heat and detoxifying.”[62] Bergenin, a volatile oil, is the main substance responsible for its pharmacological activity in the genus Rodgersia and has anti-inflammatory, antibacterial, antiviral, and immunoenhancing effects. Therefore, it is speculated that bergenin and volatile oil compounds are the main choices for Q-Markers of the genus Rodgersia.
Quality marker prediction analysis based on the measurability of chemical components
The measurability of the chemical composition is also key for the selection of the Q-Marker. HPLC was used to determine the bergenin content in R. sambucifolia and R. pinnata,[45] and the bergenin content in 350 plants of the genus Rodgersia of four species and varieties.[44] Wang et al.[63],[64],[65] established an HPLC fingerprint method to determine the composition of R. pinnata and R. sambucifolia. The results showed that these two plants contained gallic acid, bergenin, and other chemical components. The ultra-HPLC-electrochemical detector fingerprinting method was established to analyze the composition of southwest R. sambucifolia, and the results identified gallic acid, bergenin, and epicatechin gallate.[66] The diazo reagent colorimetric method was used to determine the total polyphenol content of R. aesculifolia.[67] Shen et al.[68] determined the amino acid content of R. aesculifolia using ion-exchange liquid chromatography and a Hitachi 835-30 amino acid analyzer. GC-MS has been used to analyze the volatile components[69] and determine the fatty acid content in R. aesculifolia.[70]
In summary, volatile oils, such as bergenin and gallic acid, in Rodgersia can be detected using analytical methods. These components are closely related to the bioactivities of plants of this genus and may be the main effective substances of this genus and can be used as the main choice of Q-Markers. It is advisable to further establish specific measurement methods for these components according to the differences in the various chemical components, which can provide an important basis for establishing scientific and reliable quality standards.
Conclusion and Future PerspectivesRodgersia is a traditional folk medicinal plant in China, with rich resources and wide distribution. It has great development and utilization value. However, current research on the genus Rodgersia is insufficient in both breadth and depth, and there are few studies on its chemical composition. Research on the chemical constituents and pharmacological effects of this genus is mainly concentrated on R. podophylla and R. aesculifolia. The main pharmacological research is on the extract of Rodgersia, and there are few reports on the pharmacological activity of its monomer compounds. Research on pharmacological effects mainly focuses on anti-inflammatory, antibacterial, and antioxidant properties, and few studies have been conducted on the mechanism of the pharmacological effects. Therefore, it is of great significance for the clinical application and further development of the genus Rodgersia to study its chemical constituents and pharmacological activities and establish a safe and effective quality evaluation method. This article reviews the chemical constituents and pharmacological effects of the genus Rodgersia, combined with the analysis of the genetic relationship, traditional medicinal properties, traditional efficacy, and measurability of chemical components, using predicted gallic acid, bergenin, volatile oils, flavonoids, tannins, and saponins as the main selection criteria of the Q-Marker. This provides a theoretical basis for clinical application and further research and development of Rodgersia.
Acknowledgments
Nil.
Financial support and sponsorship
This study was financially supported by the Natural Science Foundation of Hunan province (2020JJ4463, 2020JJ4064, and 2021JJ30502), Changsha Municipal Natural Science Foundation (kq2014092), and Open Fund of First-class Pharmacy Discipline of Hunan University of Chinese Medicine (2020YX02).
Conflicts of interest
There are no conflicts of interest.
References
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