OBJECTIVE

To search for new antiviral agents from traditional Chinese medicine, specifically anti-enteroviruses agents.

METHODS

The aqueous extracts (AE) of more than 100 traditionally used medicinal plants in China were evaluated for their in vitro anti-Coxsackie virus B3 activities with a MTT-based colorimetric assay.

RESULTS

The test for AE of 16 plants exhibited anti-Coxsackie virus B3 activities at different magnitudes of potency. They can inhibit three steps (inactivation, adsorption and replication) during the infection. Among the 16 plants, Sargentodoxa cuneata (Oliv.) Rehd. et Wils., Sophora tonkinensis Gapnep., Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtomium fortunei J. sm. also have activity against other enterovirus, including Coxsackie virus B5, Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated that all tested AE had CC50 values higher than their EC50 values.

CONCLUSIONS

The sixteen traditionally used medicinal plants in China possessed antiviral activity, and some of them merit further investigations.

Dry rhizome of Dryopteris crassirhizoma Nakai (Dryopteridaceae), also known as Guan Zhong, is a traditional Chinese herbal medicine used in the treatment of viral disease. But the dry rhizomes of Woodwardia JAPONICA (L. f.) Sm., OSMUNDA JAPONICA Thunb. and Cyrtomium fortunei J. Sm. are also used as Guan Zhong in local areas. The adulterants are similar to Dryopteris crassirhizoma. It is difficult to identify the botanical origin of these herbs. In our study, sequences of the cpDNA RBCL gene were determined and analyzed for Dryopteris crassirhizoma and adulterant species, where nineteen molecular markers had been determined. Also, amino acid sequences translated from the RBCL gene were analyzed and four important molecular markers were detected. Based on cpDNA RBCL and translated amino acid sequences, Dryopteris crassirhizoma can easily be distinguished from the other three fern species.

The regulation of photosystem I (PSI) redox state under fluctuating light was investigated for four species using P700 measurement and electrochromic shift analysis. Species included the angiosperms Camellia japonica, Bletilla striata and Arabidopsis thaliana and the fern Cyrtomium fortunei. For the first seconds after transition from low to high light, all species showed relatively low levels of the proton gradient (ΔpH) across the thylakoid membranes. At this moment, PSI was highly oxidized in C. japonica and C. fortunei but was over-reduced in B. striata and A. thaliana. In B. striata and A. thaliana, the redox state of PSI was largely dependent on ΔpH. In contrast, the rapid oxidation of P700 in C. japonica was relatively independent of ΔpH, but was mainly dependent on the outflow of electrons to O₂ via the water-water cycle. In the fern C. fortunei, PSI redox state was rapidly regulated by the fast photo-reduction of O₂ rather than the ΔpH. These results indicate that mechanisms regulating PSI redox state under fluctuating light differ greatly between species. We propose that the water-water cycle is an important mechanism regulating the PSI redox state in angiosperms.

Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.

Keywords: alkaloid; anti-inflammatory; anticancer; antiviral; fungus; in vitro; in vivo; neoechinulins.

In apogamous ferns, all offspring from a parent are expected to be clonal. However, apogamous 'species' frequently demonstrate a large amount of morphological and genetic variations. Cyrtomium fortunei composed of four varieties (C. fortunei var. fortunei, var. clivicola, var. intermedium, and var. atropunctatum), is all reported to be apogamous triploids, but demonstrates large and continuous morphological variation. In previous studies, we showed that considerable genetic diversity was observed in many local populations of the apogamous fern 'species'. We hypothesized that genetic segregation has occurred, because neither sexual type nor intraspecific polyploidy have been observed in C. fortunei in Japan. Of 732 progeny examined (250 gametophytes and 482 sporophytes), obtained from a parental sporophyte whose pgiC genotype was estimated as aab, 11 (4.4%) gametophytes and 8 (1.7%) sporophytes showed a different genotype (aaa) from that of the parent sporophyte. We showed that genetic segregation occurs in apogamous C. fortunei in relatively high frequency. Moreover, we could first show that the segregation frequency in gametophytes is significantly higher than that in sporophytes of the next generation (χ² = 4.90, P = 0.027). It may suggest the existence of deleterious genes, which are expressed during the morphogenesis and growth of sporophytes.

BACKGROUND

Recently, a great deal of attention has been directed toward the use of crude extracts from natural products for cosmetic applications. Thus, we performed a series of experiments to investigate skin depigmenting properties of a crude extract that was derived from a traditional Korean medicinal plant.

METHODS

In this study, the depigmentational potency of Cyrtomium fortunei J. Smith was investigated. The inhibitory effects of the root of Cyrtomium fortunei J. Smith extract on melanin production were evaluated by assessing its tyrosinase inhibitory effects, melanin production-inhibitory properties in melan-a cells and depigmenting ability in brown guinea pig skin.

RESULTS

The methanolic extract of the root of Cyrtomium fortunei J. Smith appeared to inhibit tyrosinase activity and melanin production in melan-a cells. In addition, this extract exhibited depigmenting ability on Ultra violet-induced hyper pigmentation in brown guinea pig skin.

CONCLUSIONS

These results suggested that root of Cyrtomium fortunei J. Smith might prove useful in treating skin hyperpigmentation associated with excess sun-exposure.

The wormicidal effect on Clonorchis sinensis in boiled water extracts of 223 species (vegetable origin 206, animal origin 10, mineral origin 7) of raw drugs prescribed in Oriental medicine was observed in vitro. The wormicidal substances were detected from 31 of the above-mentioned species. The wormicidal substances extracted from Platycodon grandiflorum (radix), Schizandra chinensis (fruit), Polygala tenuifolia (herb) and Aster tataricus (radix) were most effective. Those from Smilax glabra (radix), Pueraria thunbergiana (flower, radix), Polygala tenuifolia (radix), Scutellaria baicalensis (radix), Prunus mume (fruit), Glycyrrhiza uralensis (radix), Angelica koreana (radix), Phytolacca esculenta (radix) and Cyrtomium fortunei (rhizoma) were effective. The rest of the raw drugs were less effective.

To identify plants with potential application in phytoremediation, the concentration of cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), lead (Pb), and zinc (Zn) in soil and 14 dominant plants sampled from a lead-zinc mining area in Nanjing City was measured. Furthermore, the heavy metal contamination of soil, and bioaccumulation and translocation of the 6 heavy metals by the 14 plants were evaluated. The results showed that the principal contaminants were Cd, Mn, Zn, and Pb, and their single factor pollution index was 45.71, 11.68, 10.40, and 4.46, respectively. Furthermore, the Nemerow index of this area was 33.45, which indicated that the mining area was severely polluted. All the 14 dominant plant species were metal-tolerant, although the concentration of metal varied between different spices. Among them, Pteris multifida and Trachelospermum jasminoides significantly accumulated the heavy metals. The concentration of Zn in all the dominant plants was beyond the normal range; however, the bio-concentration factor (BCF) of only Digitaria sanguinalis for Zn was>1, while the BCF of the remaining species for the 6 heavy metals was<1. Furthermore, the heavy metal bio-transfer factor (BTF) of the 14 species was generally high. The BTF of Helianthus tuberosus and Dendranthema indicum for the 6 heavy metals was>1. According to the mechanism of heavy metal accumulation, the 14 plant species were classified into 3 types:accumulators (H. tuberosus, D. indicum, Phytolacca americana, Justicia procumbens, D. sanguinalis, Sonchus brachyotus, Solanum nigrum, and Setaria viridis), root compartment (P. multifida and T. jasminoides), and excluders (Solidago decurrens, Duchesnea indica, Carex breviculmis, and Cyrtomium fortunei).

The complete chloroplast genome of an important medical fern Cyrtomium fortunei has been sequenced. Its genome is 151,699 bp in length with a pair of inverted repeats (IRs, 23,875 bp), separated by a small single copy region (SSC, 21,625 bp) and a large single copy region (LSC, 82,324 bp). It contains 132 genes, covering 88 protein coding genes, 35 tRNA genes, eight rRNA genes, and one pseudogene. Maximum likelihood analysis indicates that the phylogenetic tree is monophyletic with three clades. Cyrtomium fortunei is closely related to C. devexiscapulae, which further forms a sister clade to C. falcatum.

Keywords: Cyrtomium fortunei; chloroplast genome; medical fern; phylogenetic analysis.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens (Realgar [Xionghuang], Cyrtomium Fortunei J. Sm[Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi (Astragali Radix [Huangq], Glycyrrhizae Radix et Rhizoma [Gancao]) are used for modern prevention. Taking CHM that expel pathogens (Realgar [Xionghuang], Lonicerae Japonicae Flos[Jinyinhua]) and CHM eliminating dampness (Atractylodis Rhizoma [Cangzhu], Pogostemonis Herba[Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.

Keywords: COVID-19; Chinese Herbal Medicine (CHM); Chinese Medicine (CM); Epidemics; Herbs; Infectious Diseases; Pestilence; Prevention; Review.