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REVIEW ARTICLE
Year : 2023 | Volume
: 9
| Issue : 1 | Page : 1-7
Traditional uses and phytochemical constituents of Cynanchum otophyllum C. K. Schneid (Qingyangshen)
Christian Bailly1, Cheng Xiang2, Ji-Hong Zhang3
1 Oncowitan, Scientific Consulting Office, Lille (Wasquehal), 59290, France
2 Faculty of life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
3 Medical School, Kunming University of Science and Technology, Kunming 650500, China
Correspondence Address:
Christian Bailly
Oncowitan, 59045 Lille (Wasquehal)
France
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.353189
The roots of the plant Cynanchum otophyllum C. K. Schneid (Apocynaceae), known as Qingyangshen in Chinese, are used for a long time as a traditional medicine by different ethnic communities in the Yunnan province (China). The multiple properties and applications of this herbal medicine have been analyzed. C. otophyllum is a perennial herbal liana, nonedible, and generally wild harvested. A cultivation method has been proposed to increase the fruit set level. Qingyangshen is used essentially to treat epilepsy, rheumatism, or other inflammatory diseases. The plant can be found also in diverse polyherbal preparations used in cosmetic or as food supplement (detox products), and in phyto-preparations claimed to reduce hair loss. The plant is a rich reservoir of C-21 steroidal glycosides. Many bioactive compounds have been isolated from this plant and some of them have been pharmacologically characterized, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, all briefly evocated here. The plant presents also interesting features in other domains. In particular, leave extracts of C. otophyllum C. K. Schneid contain proteases which are exploited for the local preparation of a cheese-like milk cake. Qingyangshen herbal preparation can be useful to treat epilepsy and inflammation. It has applications beyond medicine in the cosmetic and food industry.
Keywords: Cynanchum, epilepsy, medicinal plant, steroidal glycosides
In the Apocynaceae family, the genus Cynanchum (common name swallow-wort) includes about 300 plant species (295 species cited in The Plant List (http://www.theplantlist.org), with an accepted name status), including twining herbs, sub-shrubs, and invasive weeds in some cases. These plants can be found everywhere, in Asia, Africa, Europe, and the Americas, in tropical and subtropical areas of all continents. Cynanchum is among the groups with the most important variability in shape and composition.[1] They have no highly specific morphological characters and for this reason, it is not always easy to identify the right plant in this taxus. Many of these species have similar morphological features, which complicate their identification. In some cases, the nomenclatural status of the plant has been debated.[2] A phylogenetic analysis of the chloroplast genome is sometimes necessary to correctly identify the plant.[3] A DNA barcoding has been developed, on the basis of the internal transcribed spacer 2 barcode,[4] to help identification. It is a technically sophisticated method, with a nonnegligeable associated cost, but it can be useful to guarantee an accurate identification of the herbal medicine, in order to protect the consumers. Spectroscopic methods can be used also to distinguish two species. For example, the root part of Cynanchum auriculatum has been misused for C. wilfordii in herbal drug markets in Korea due to their morphological similarities. A spectroscopy technique has been proposed to distinguish these two species.[5]
There are about 60 Cynanchum species in China, 19 of which are used as herbal medicines (http://frps.eflora.cn/frps/Cynanchum).[6] The most popular species are arguably C. bungei Decne, C. auriculatum Royle ex Wight. and C. wilfordii (Maxim.) Hemsl. which are well-known Chinese herbal medicines collectively known as Baishouwu.[7]C. paniculatum (Xuchangqing) is also a commonly prescribed traditional Chinese medicine for the treatment of various inflammatory diseases.[8],[9] Another one is C. thesioides, used in traditional Mongolian medicine to treat abdominal pain and diarrhea.[10] Other Cynanchum species of medicinal interest could be cited. In 2018, an excellent review has inventoried the most popular traditional prescriptions including Cynanchum species and their essential phytochemical constituents.[11] Here, we will focus on a specific species, called Cynanchum otophyllum C. K. Schneid, or under its Chinese name Qingyangshen (or Qing Yang Shen, QYS) [Figure 1]. The objective of this short review is to provide an update on the traditional and modern uses of this plant, the derived products, and recently isolated bioactive natural molecules.
Figure 1: The plant Cynanchum otophyllum C. K. Schneid and pieces of the dried roots. The plant is also named Cyathella otophylla (C. K. Schneid.) C. Y. Wu and D. Z. Li or Vincetoxicum otophyllum (C. K. Schneid.) P. T. Li. The plant can be found essentially in the Yunnan province of China, and all along South China. The two photos on the left were taken in Lijiang (Yunnan) by Dr Cheng Xiang. The top right photo comes from Flora of China (http://www.efloras.org/object_page.aspx?object_id = 52143andflora_id = 2) Cynanchum otophyllum and its Traditional Use in Chinese Medicine This herbaceous plant is endemic to the Yunnan province of China, but it can be found in a variety of temperate habitats from Tibet to South China. C. otophyllum is a perennial herbal liana [Figure 1] but only the dried roots are used in traditional medicine, generally as decoctions to treat epilepsy, rheumatism or used as tonic for the blood system. The traditional use also refers to alcohol extracts drank to treat varicose veins and to cooked preparations with chicken.[12],[13] The plant is used by different ethnic communities in the Yunnan province. Notably, it is used by the Yi community in Mile City as a tranquilizer and to treat stomachache, epilepsy and madness. The plant Yi name is “cinazai” or “roujiboqi.”[14],[15] Similarly, the plant is used by the traditional Yao, to treat epilepsy, urticaria, tinnitus and bone ache caused by rheumatoid. In this case, the local Yao name of the plant is “qing yang pei.”[15] In the west of Yunnan, Dali and Lijiang, Naxi and Bai communities use the root of C. otophyllum to treat epilepsy, indigestion and rheumatism.[16] The Tibetans in Shangri-la (a biodiversity hotspot of the Yunnan province) also use the plant (which they call “ba be da”) to treat rheumatism.[17] Qingyangshen is used for a long time in Traditional Chinese Medicine to treat epilepsy, lumbar muscle strain, as well as rheumatism in southwestern China.
Qingyangshen is usually collected locally from the wild habitats, but the resource is sometimes limited and as mentioned above, the plant identification is not always easy. In addition, there could be quality problems, such as pollution of the environment where the medicinal plant grows. Nevertheless, the collect of wild plants is important, not only to provide food and nutrients to local people but also as a source of cash income.[18] Although qingyangshen is not an edible plant, attempts have been made to cultivate the plant to facilitate its supply. The cultivation of C. otophyllum is not easy because the plant produces bountiful flowers but not all of them mature into fruits. It has been estimated that the level of self-pollinated flowers is only 1.5%. A cultivation method has been introduced and it has permitted to increase the fruit set level in cross-pollinated flowers to about 12.6%. Honeybees (Apis cerana Fabricius) are the main pollinators for this plant.[19] The culture of the plant could be further developed. Tissue cultures of C. otophyllum are also possible but rarely used.[20] Culture from the callus of the plant has been established and various classical natural products (oleanic acid, betulinic acid, and daucosterol) have been isolated from these plant cell growths.[21] Reports on the in vitro cultures of Cynanchum species are limited.[22],[23]
Herbal Products Made from Cynanchum otophyllumC. otophyllum is used alone or combined with other medicinal plants. For example, the plant is included in the formula of Heqi San used to treat polycystic ovary syndrome. It is a complex preparation made of 12 plants, including C. otophyllum to regulate the innate immune system, to protect the liver and to contribute to the anti-inflammatory action.[24] Phyto-preparations used to treat alopecia can also contain C. otophyllum, such as Yangxue Shengfa capsule and Bushen Yangxue capsule, two products composed of C. otophyllum and recommended for the treatment of hair loss.[25] The traditional prescription Baiwei wan and Anwei jian also include the plant C. otophyllum and they are used to treat irregular menstruation and stomach pain, respectively.[11]
The plant is used in a polyherbal preparation (made from 9 plants) called “Pai Du Yang Yan Pian”, a tablet formulation considered as a “Beauty Detox” product for the treatment of acne. Another detox product named BandH360 containing C. otophyllum and two other plants (radix Panax and Rubia Yunnanensis Diels) can be found. A few years ago, there was also a product named Qingyangshen Tablets (developed in 1984 by Lijiang Pharmaceutical Co., China) made from the total saponin extract of C. otophyllum.[26] A method for the preparation of C. otophyllum dispersible tablets was patented in 2009.[27] But today, this over-the-counter product does not seem to be available anymore. Nevertheless, over the past few years there was a renewed interest in the use for this medicinal plant with the identification of a diversity of bioactive molecules. A recent patent has reported the method for the preparation of C. otophyllum wall-broken decoction pieces for the treatment of epilepsy and chronic hepatitis.[28]
Pharmacological Effects of Cynanchum otophyllum Extracts and their Bioactive ComponentsExperimental studies published in the 1980-1990s have evidenced the capacity of Qingyangshen to reduce epileptic seizure, convulsion and to modulate the development of brain and memory behavior in rat models [Figure 2].[29],[30],[31],[32] These observations were largely confirmed later, highlighting the neuroprotective effects of these compounds.[33],[34],[35] Extracts of the plant have revealed anti-depressant effects in animal models,[36] an activity observed with other Cynanchum extracts, such as C. auriculatum Royle ex Wight.[37] In addition, C. otophyllum has revealed antifungal, anti-inflammatory and immunomodulating properties, attributed to a variety of bioactive natural products included in the plant extracts. Over the past 20 years, numerous natural products have been isolated from C. otophyllum, notably a large number of steroidal glycosides. A comprehensive phytochemical analysis of C. otophyllum has been reported in 2018.[11] The authors inventoried a large series of compounds called otophyllosides A-to-Z, as well as several caudatin glycosides and qingyangshengenin glycosides. Pregnane glycosides are abundant in C. otophyllum.[38],[39],[40],[41],[42],[43],[44] There was also gagaminin and rostratamine glycosides, plus a short series of compounds called cynotophyllosides A-to-H, and a few other compounds, all isolated from the roots of the plant. Altogether, more than sixty C-21 steroidal glycosides have been isolated from the plant. There are certainly more compounds to discover. Among these compounds, cynanotosides A, B and cynotophylloside H showed significant dose-dependent protection from homocysteic acid-induced oxidation stress. Otophylloside B showed neuroprotective effect in a model of Alzheimer's disease and otophyllosides A, B, and F inhibited seizures.[11],[45] The neuroprotective effects of Qingyangshen and potential use of the plant extract for the treatment of Alzheimer's disease has been recently highlighted. The oral administration of Qingyangshen extract to mice has been found to improved learning and spatial memory.[46]
Figure 2: A schematic illustration of the beneficial effects of Cynanchum otophyllum extracts or specific compounds isolated from the plant on central pathologies such as depression and epilepsy. The main bioactive compounds are indicatedOver the past 2 years, a few more natural products have been discovered from Qingyangshen extracts, such as a novel series of eight C-21 steroidal glycosides designated cynanotins A-H [Figure 3]. Some of them were found to exhibit a very mild cytotoxic activity against HL-60 leukemia cells.[47] A more pronounced cytotoxic activity was evidenced with another series of C21-steroidal aglycones named cynotogenins A-I.[48] The chemical diversity is huge, as illustrated with the recent identification of another novel series of seven C-21 steroids named cynanchin A-G with hepatoprotective effects,[49] as well as a series of seven polyhydroxypregnane glycosides named cynotophyllosides P-V.[50] Interestingly, the derivative cynotophylloside R [Figure 3] was found to promote the proliferation of concanavalin A-stimulated splenocytes at low concentration (0.01 and 0.1 mg/ml) but to inhibit the proliferation of the same cells at higher concentrations.[50] Depending on the methods and solvents used for extraction, different types of compounds can be isolated from Cynanchum species.[51] Novel methods of ultrasonic extraction of C. otophyllum aglycones have been patented recently.[52] There is no doubt that the development of innovative discovery methods will continue to yield compounds with unique structural and biological properties in this plant family. Here we focused our analysis essentially on steroidal glycosides but the plant also contains a variety of benzophenone derivatives,[53] as well as carbohydrates[54],[55] and polysaccharide sulfate [Table 1].[56]
Figure 3: Chemical structure of selected compounds isolated from Cynanchum otophyllum C. K. Schneid. The C-21 steroidal aglycone qingyangshengenin (CID: 435955, C28H36O8), the steroidal glycosides otophylloside N, cynanchin E,[49] cynanotin E (kidjoranin-3-O-b-D-cymaropyranosyl-(1 → 4)-b-D-cymaropyranoside),[47] cynotophylloside R (kidjoranin 3-O-a-L-cymaropranosyl-(1 → 4)-a-L-diginopyranosyl-(1 → 4)-b-D-cymaropranoside),[50] and cynotogenin D.[48] The compounds have been obtained using either conventional heat-reflux extraction methods, organic solvents, or an aqueous ionic liquid based ultrasonic assisted extraction method Nonmedical Uses of Cynanchum otophyllum The aerial parts of C. otophyllum are not edible. The roots are sometimes cooked (certainly to remove the bitterness) but there is no mention for the leaves or the fruits, apparently not consumed. However, the leaves can be used traditionally (notably in the JianChuan and HeQing counties of Yunnan province) to produce a kind of cheese, called milk cake, as a soft curd. This traditional cheese is obtained by soaking a solution of C. otophyllum leaves with milk [Figure 4]. The active coagulant components (proteases) have been identified and the conditions to improve milk-clotting have been determined.[62] Two proteases have been partially purified and their milk-clotting activities were biochemically characterized. These are two cysteine proteases, able to hydrolyze β-casein and κ-casein completely, and α-casein partially. Their milk-clotting activities are limited compared to conventional calf rennet, but they could offer an alternative to prepare milk cake and cheeses.[63] Other cysteine proteases have been identified from Cynanchum species, notably from C. puciflorum.[64]C. otophyllum leaves can be used as a rennet substitute in cheese-making. Other applications of C. otophyllum in the food industry and agriculture are being investigated. For example, a recent Chinese patent refers to the use of a spray solution of the plant to improve storage and preservation of onions.[65]
Figure 4: Schematic illustration of the use of Cynanchum otophyllum extracts to prepare a traditional cheese Conclusion The plant C. otophyllum C. K. Schneid (Qingyangshen) is largely distributed but used as a traditional medicine essentially in the Yunnan province of China. There is no mention of the traditional use of the plant roots in other countries, even if the plant can be found in many places worldwide. Qingyangshen is a rich reservoir of C-21 steroidal glycosides. These natural products are at the origin of the medicinal activities reported with this plant and diverse phyto-preparations. Over the past 15 years, important studies have been devoted to the identification of new natural products. They have permitted to isolate many compounds, such as otophyllosides, cynotophyllosides, cynanotins, cynotogenins, cynanchins, and others.
The mechanism of action of these compounds and their molecular targets has been little investigated thus far. Effort should be directed now at better characterizing their activity and toxicity profiles. Important studies are emerging, such as a recent characterization of the benefit of Qingyangshen to improve cognitive function in mice.[46] The compounds at the origin of the neuroprotective effects of the plant are being characterized, such as otophyllosides B and N.[57],[58] These compounds, together with other C-21 steroidal glycosides, are being increasingly recognized as neuroprotective agents.[66] The use of Qingyangshen for the treatment or prevention of cognitive dysfunction and cognitive decline should be encouraged. There is a need for further in vivo studies aimed demonstrating the activity of the phytochemicals and their safety for use in human. Moreover, Qingyangshen is not only a great medicinal plant, but it exhibits also useful properties for the cosmetic (beauty detox product) and food industry, notably for the preparation of cheeses. This little-known plant deserves further attention.
CRediT authorship contribution statement. Christian Bailly: Conceptualization; Investigation; Visualization; Writing-original draft; Writing-review and editing. Cheng Xiang: Investigation; Writing-review and editing. Jihong Zhang: Investigation; Writing-review and editing.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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