[Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26] Download free from www.wjtcm.net Review Article

Reviewing Threats to Wild Rhodiola sachalinensis, A Medicinally Valuable yet Vulnerable Species

Josef A. Brinckmanna, Anthony B. Cunninghamb,c, David E. V. Harterd aTraditional Medicinals, Sustainability Department, 4515 Ross Road, Sebastopol, California, 95472, USA, bSchool of Life Sciences, University of KwaZulu-Natal, King Edward Avenue, Pietermaritzburg, 3209, South Africa, cSchool of Veterinary and Life Sciences, Murdoch University, 90 South St., Murdoch, WA, 6150, Australia, dBundesamt für Naturschutz (BfN), Konstantinstr. 110, Bonn, 53179, Germany

Abstract

Occurring in China, DPR , Japan, and Russian Federation and classified in the Red List of Chinese Flora as a vulnerable species, Rhodiola sachalinensis Boriss. is used increasingly in cosmetics, dietary supplements, and Traditional Chinese Medicines (TCMs). The aim of this study was to evaluate the (i) conservation status, harvesting and trade levels of R. sachalinensis, (ii) current state of experimental and commercial farming, and (iii) evidence of substitution or interchangeable use of R. sachalinensis with other Rhodiola species. We assessed data from multiple disciplines and languages including studies on R. sachalinensis biology and ecology, information on impacts of wild harvest, management measures, and current levels of cultivation. Our assessment shows that while R. sachalinensis is increasingly produced by cultivation, wild populations are decreasing and face multiple threats. These include (a) habitat loss including due to oil and gas infrastructure development on Sakhalin island, (b) climate change impacts on alpine ecosystems, and (c) overexploitation of wild plants to satisfy the growing commercial demand. Assessments of the conservation status of R. sachalinensis should commence in each Range State, as well as resource assessments and monitoring of harvesting and trade of wild R. sachalinensis. Even with increased reliance on cultivation, biodiversity conservation, and genetic diversity in wild populations are relevant to future use of this species.

Keywords: Conservation, Rhodiola rosea ssp. sachalinensis, Rhodiola sachalinensis, sustainable production, Traditional Chinese Medicine

Introduction measures, and on the current level of cultivation. Our data collection strategy involved using a group of search terms in Rhodiola sachalinensis Borissova, Crassulaceae multiple languages (Chinese, English, Japanese, Korean, and (“gaoshanhongjingtian” (高山红景天), high mountain rhodiola Russian). Search terms included R. sachalinensis, traditional or “kuyehongjingtian” (库页红景天), Sakhalin rhodiola), is a medicine, wild collection, cultivation, export trade, harvesting, rare species with a fragmented distribution[1] in China, DPR conservation status, protected, threatened, red list, and red Korea, Russian Federation, and Japan.[2] R. sachalinensis has book. We used the online academic search engine Google become a popular Rhodiola species[3] traded in Traditional Scholar, China Academic Journals (CNKI) database, and Chinese Medicine (TCM) markets[4] and is also widely used ResearchGate, a professional network for scientists and in dietary supplements[5] and cosmetics. However, there are researchers, as well as patent databases of the China National conservation concerns about this vulnerable (VU) species.[6,7] Intellectual Property Administration, Korean Intellectual This study evaluates the (i) conservation status, harvesting, and trade in R. sachalinensis, (ii) current cultivation, and Address for correspondence: Prof. Josef A. Brinckmann, (iii) evidence of interchangeable use of R. sachalinensis with Traditional Medicinals, Sustainability Department, 4515 Ross Road, other Rhodiola species. Sebastopol, California 95472, USA. E‑mail: [email protected] Methods This is an open access journal, and articles are distributed under the terms of the Creative We reviewed published studies on R. sachalinensis biology and Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, ecology, information on impacts of wild harvest, management tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Access this article online For reprints contact: [email protected]

Quick Response Code: © 2021 World Journal of Traditional Chinese Medicine | Published by Wolters Kluwer ‑ Medknow Website: www.wjtcm.net Received: 16‑02‑2021, Accepted: 31‑03‑2021, Published: 09-08-2021

DOI: How to cite this article: Brinckmann JA, Cunningham AB, V. Harter DE. 10.4103/wjtcm.wjtcm_47_21 Reviewing threats to wild Rhodiola sachalinensis, a medicinally valuable yet vulnerable species. World J Tradit Chin Med 2021;7:299-306.

World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 299 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

Property Office, United States Patent and Trademark Office, differences between R. sachalinensis and R. rosea are and World Intellectual Property Organization. For information described. Third, while R. rosea has a circumpolar distribution, on R. sachalinensis occurrence, conservation, legal, and R. sachalinensis has a much more limited geographic regulatory status, we searched the websites and databases of distribution in , DPR Korea, small parts of governmental organizations such as ministries of agriculture, Japan, and the Russian Far East. environment, health, medicines, natural resources and ecology, Chemistry and medicinal uses and tourism, respectively. The root and rhizome of R. sachalinensis contain phenylpropanoids such as the cinnamyl alcohol glycosides Results rosarin and rosavin, the phenylethanoid compound salidroside Taxonomy with its aglycone tyrosol, flavonols such as rhodionin While “The Plant List”, Version 1.1. (2013) treats R. sachalinensis and rhodiosin,[14] monoterpene glycosides (sachalosides I Borissova as a synonym of Sedum roseum (L.) Scop,[8] and the and II), flavonol bisdesmosides (sachalosides III and IV), International Crassulaceae Network lists R. sachalinensis and cyanogenic glycosides (sachaloside V).[15] The Borissova, Sedum sachalinense (Borissova) Voroschilov, and provincial standards for TCM materials require the herbal Rhodiola rosea ssp. sachalinensis (Borissova) S. Gontcharova drug “Rhodiolae Sachalinensis Radix et Rhizoma” to contain as synonyms of R. rosea L.,[9] Chinese authorities on botany, not‑less‑than (NLT) 0.20% of salidroside and NLT 0.020% of [16] taxonomy, threatened species, and TCM treat R. sachalinensis tyrosol, calculated on a dried drug basis. Less specifically, as a distinct article; for example, botanists at Flora of China,[2] the Zhejiang provincial standards for TCM materials require and at the Ministry of Environmental Protection and Chinese pharmacopoeial quality R. sachalinensis to contain NLT 22.0% [17] Academy of Sciences (Red List of Chinese Flora),[6] as extractive matter and NLT 6.0% total rhodiola glycosides. well as pharmacognosists at provincial TCM drug product According to TCM theory, R. sachalinensis root and rhizome administrations. Regardless of some differing taxonomic acts to invigorate qi and promote blood circulation and is opinions, in China, R. rosea and R. sachalinensis are classified indicated for treating conditions such as qi deficiency and blood and traded as separate articles of commerce, sourced from stasis, chest pain, angina, stroke, hemiplegia (paralysis of one [16] separate geographic origins, R. rosea from Xinjiang and side of the body), fatigue, asthma, and panting. R. sachalinensis from Jilin and Heilongjiang, each with distinct Ecology and distribution characteristics described in monographs. As we reported The habitat of R. sachalinensis is described as forested slopes, [10] earlier in Cunningham et al., we treat R. sachalinensis as gravel slopes, and alpine tundra in northeastern China (Jilin, a distinct species for three reasons. First, chemotaxonomic Heilongjiang), DPR Korea, Russian Federation, and Japan,[2] [11] [12] studies by Booker et al. and Liu et al., show chemical as well as in rock crevices and stony sites on some volcanic differences between R. rosea (collected in Xinjiang) and oceanic islands of Japan and the Russian Federation.[18] R. sachalinensis (collected in Heilongjiang and Liaoning). While the observed differences in Liu et al.,[12] using a high performance In China, R. sachalinensis is distributed mainly in the liquid chromatography‑diode array detection and ultraviolet Changbai of northeastern Jilin province spectrophotometric (HPLC‑DAD/UV) method, based on [Figure 1], and Heilongjiang province in the Zhangguangcai [19] [20] eight compounds of four chemical classes (phenylpropanoids, Mountains and Daxingan Mountains. It is found, in phenylethanol derivatives, flavonoids, and phenolic acids) the Yanbian Korean Autonomous Prefecture of China’s [21] were only weak, Booker et al.,[11] using general metabolomic Jilin Province, which borders both Primorsky Territory, fingerprinting but also specific high‑performance thin‑layer Far Eastern Federal District, Russian Federation, as chromatography (HPTLC) methods for testing of the rosavin well as the northernmost province of DPR Korea, North and salidroside marker spectra, found compelling differences Hamgyong Province. In the Nature between R. rosea and R. sachalinensis samples. In a DNA Reserve (CMNR), R. sachalinensis is recorded at an altitude [22] barcoding study of six Rhodiola species, Zhang et al.[13] range of 1600–2500 m above sea level (a. s. l.) and shares habitat with “changbaihongjingtian” (长白红景天, Rhodiola were able to identify and differentiate five of the six species [5] including R. sachalinensis. Their analysis showed that five angusta Nakai). In DPR Korea, R. sachalinensis occurs in the accessions of R. rosea, obtained from different locations, Mountain Range, growing in cracks near the formed a clade (evolved from a common ancestor) with their tops of Mountains Paekdu, an active super , between 1800 and 5000 m a. s. l., as well as on Mountains Potae and only accession of R. sachalinensis as well as with one accession Mountains Rangrim.[23,24] of R. tangutica (Maxim.) S. H. Fu (唐古特红景天‑Tangut hong jing tian), noting that R. rosea and R. sachalinensis have It is reported to occur on Island (a disputed territory strong morphological similarity. Second, treating R. rosea and claimed by Japan and )[25] and on the uninhabited Ekarma R. sachalinensis as distinct species fits with the taxonomic Island (Russia), which consists of two overlapping volcanoes perspectives of Flora of China,[2] and of Qin et al.[7] (threatened reaching 1170 m a. s. l.,[26] near the center of the species list of Chinese higher plants), among other Chinese and chain in the Sea of Okhotsk. Furthermore, the species occurs Korean scientists. In the Flora of China, some morphological on the Habomai islets (disputed territory between Japan and

300 World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

Russia), in the southernmost Kuril Islands,[27] and on the was elaborated further to a classification of “VU B1ab (i, iii); Russian islands of Sakhalin and Moneron.[28] On Sakhalin D1”.[7] Criteria VU B1 means that the extent of occurrence in Island, one of the largest islands in the boreal zone of the China is <20,000 km2. Furthermore, VU B1ab means that the Pacific Ocean, R. sachalinensis occurs in ten of 13 recognized geographic range is severely fragmented or that there are less geobotanical areas, sharing habitat with R. rosea in eight of than ten locations where the species is known to occur and that the 13 areas. In common with many other Rhodiola species, continuing decline is observed, estimated, inferred, or projected R. sachalinensis appears to favor habitat near perennial in (i) extent of occurrence and (iii) quality of habitat. The streams.[29] additional designation of VU D1 means that the population is very small or restricted or that the number of mature individuals R. sachalinensis is a long‑lived, dioecious perennial that flowers is <1000.[33] Table 1 summarizes the conservation status of wild between April and June and fruits from July to September. R. sachalinensis in the countries where it reportedly occurs. Regeneration is primarily from seed, although clonal sprouting from the rhizome is also likely to take place. The challenge Several factors are affecting the habitats where R. sachalinensis posed by commercial harvesting is that removing whole occurs, even within protected areas. On Sakhalin Island, plants (or entire rhizomes) prevents both reproduction from seed economic development has been focused on resource and through clonal sprouting. R. sachalinensis is known to be extraction (forestry, fisheries, coal, oil, and gas), particularly an outcrossing, insect pollinated species with wingless seeds.[30] since the mid‑1990’s.[39] Infrastructure development associated Based on Random Amplified Polymorphic DNA analysis using with the oil and gas industry has directly influenced Rhodiola 106 markers, a genetic difference has been discerned between habitat. Plans for the 800 km long onshore pipeline, proposed R. sachalinensis plants from the Changbai Mountains compared as a part of the “Sakhalin II Phase 2” development project, to those in the Daxinganling Mountains.[20] envisaged transport of oil and gas from the oil fields on the northeast of the island to Aniva Bay in the south, crossing Furthermore, R. sachalinensis is known to be associated two nature reserves, Makarovsky Reserve and Izubrovy with 29 genera of endophytic fungi, some with economic Reserve, where Rhodiola species occur. The Environmental potential as sources of novel antioxidant substances. Fifteen Impact Assessment (EIA) for this pipeline development of these endophyte genera were found exclusively on was concerned about the following effects on habitat: “soil R. sachalinensis compared to R. augusta and R. crenulata erosion and compaction, physical disturbance to surface (Hook.f. & Thomson) H.Ohba.[5] A loss of wild populations watercourses, contamination of groundwater, due to release of of R. sachalinensis could also result in a loss of certain sewage treatment plant effluent and hydrotest waters, habitat endophytes, along with their potential health benefits loss and fragmentation, and direct impacts to protected or Threats and trends rare species of fauna and flora.”[28] Furthermore, radioactive Human‑induced threats are highly significant for several contamination of vegetation on Sakhalin Island due to fallout reasons. These include habitat loss due to infrastructure from the Fukushima Nuclear Power Plant in Japan might be developments by the oil and gas industry,[31] habitat loss due an issue of concern. It has been shown that 137Cs levels were to drying of streams and seepage areas, and encroachment by higher in mosses and lichens compared to herbaceous and trees able to move to higher altitudes with a warmer climate,[32] woody plants;[40] however, further monitoring of wild harvested and commercial exploitation. For example, Yan et al.[30] point R. sachalinensis from the Sakhalin Oblast may be advisable, out that: “The economic value of the plant has resulted in given the human consumption of this species. heavy collections in recent years, which induced its limited The CMNR, which was declared in 1960, forms part of the distribution and fragile habitat.” Changbai Mountain Biosphere Reserve (CMBR)[41] and is While R. sachalinensis was classified as VU in the 2013 Red considered to be well protected.[42] At a landscape scale, List of the Chinese Flora,[6] in the 2017 revision, its status however, Ma et al.[43] showed that only 25.3% of protection

Table 1: Conservation status of Rhodiola sachalinensis Range state Conservation status References China, PR R. sachalinensis is classified as VU in the 2013 red list of the Chinese Flora and as VU B1ab (i, iii); D1, in the 2017 [6,7] elaboration of the revised red list Japan Not included in the 2020 red list of Japan [34] Korea, DPR R. sachalinensis is not included in the 2005 red book of DPR Korea. Three Rhodiola species are listed, each as NT; [35] (1) Rhodiola angusta Nakai, (2) R. elongata (Ledeb.) Fisch. and C.A.Mey., and (3) R. ramosa Nakai Russian Not included in the red book of the Russian Federation. While R. sachalinensis occurs in the Russian Far East, it is not [36‑38] federation included in the red book of Primorsky Territory, where both R. komarovii Boriss and R. rosea are listed as EN. Nor is it listed in the red book of Sakhalin region, where Rhodiola isсhidae (Miyabe et Kudо) H. Hara is listed in category 3d (rare with limited area) and R. rosea in category 3b (rare with a small number of populations over a large area) VU: Vulnerable, NT: Near threatened, EN: Endangered, R. rosea: Rhodiola rosea, R. sachalinensis: Rhodiola sachalinensis, R. ramosa: Rhodiola ramosa, R. elongata: Rhodiola elongata, R. komarovii: Rhodiola komarovii

World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 301 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

Figure 1: A map showing the recorded geographic distribution of Rhodiola sachalinensis in yellow. This range extends from the type locality in the Russian Far East (Sakhalin Island) to the Changbai Mountains that span the border of China and DPR Korea, as well as the Kuril islands north of Hokkaido, Japan. Map content informed by Global Biodiversity Information Facility data, Kunming Institute of Botany iFlora database, Gage et al. (2006), Sundukov and Sundukov (2020), and for Sakhalin Island, herbarium specimens

objectives had achieved their conservation targets and Trade concluded conservation efficiency was low. Infrastructure Utilization development associated with tourism on both the Chinese R. sachalinensis has become one of the most popular and North Korean sides of the border have also affected TCM materials obtained from Rhodiola species.[47] Official habitats on the mountain. As have infrastructure for bottled monographs for its use in TCM are published by provincial water from the Paektu Spa and for military installations on drug administrations.[16,17] Moreover, as such, the herbal drug the North Korean side. “Rhodiolae Sachalinensis Radix et Rhizoma” is traded at The effects of climate change also pose a challenge. TCM markets such as the Hebei Anguo Medicinal Material [4] A dendrochronology study in the Zhangguangcai Mountains, Market. R. sachalinensis also ranks among the most widely over a 211‑year period (1803–2013) showed that northeast used Rhodiola species in dietary supplement products.[5] China has been affected by climate oscillations in the Yanbian University (Yanbian Korean Autonomous Prefecture, past, which might increase with current global warming, Jilin) holds a Chinese patent for production of a health potentially reducing habitat suitability for R. sachalinensis.[32] food supplement product in the form of dispersible tablets While no studies have modeled impacts of climate change containing an extract of R. sachalinensis with hypoglycaemic on R. sachalinensis populations, the implications of climate function.[48] The Chinese biotechnology company Taizhou change, described by You et al.,[44] for declining habitat Danding Biotechnology Co., Ltd. (Taizhou, Jiangsu) suitability for other high altitude Rhodiola species may be holds a U. S. patent, describing methods for extracting applicable. the pharmacologically active substance herbacetin from R. sachalinensis and other Rhodiola species.[49] Res Green Human impacts on R. sachalinensis fit in with trends in Biological Engineering Group Co., Ltd (Liuyang, Hunan) commercial exploitation in relation to other Rhodiola species. holds a Chinese patent for production of a topical body milk For example, based on fieldwork in China, Jiang et al.[45] product, composed mainly of an extract of R. sachalinensis considered that R. sachalinensis was “on the edge of extinction root, indicated for use as a skin moisturizer, to slow down due to constant consumption and the disturbance of the skin aging, and restore skin elasticity.[50] In Republic of Korea, habitats.” Based on their fieldwork on Changbai Mountain a extracts of R. sachalinensis are used as hair‑ and skin‑care decade later, Yan et al.[46] supported this concern about wild functional components of cosmetic products.[24] R. sachalinensis populations. While the Red List of Chinese Flora classification is “VU B1ab (i, iii); D1”[7] both Yan et al.[30] Legal trade and Zhao et al.,[1] in their studies on the genetics of wild and Quantifying the level of international trade was not possible ex situ populations, considered this species endangered. because there are no known species‑specific harmonized

302 World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

system tariff codes (HS Codes) assigned in any country for northernmost part of the Baekdudaegan Mountain Range any commercial forms of this species. Because it is reported that stretches over 1400 km from Mountains Paektu at that “gaoshanhongjingtian” (高山红景天, R. sachalinensis) the Chinese/DPR Korean border to Mt. Jiri in Republic of may be traded, intentionally or unintentionally, as a substitute Korea,[54] the cultural significance of this mountain range in for “dahuahongjingtian” (大花红景天, Rhodiola crenulata) or both DPR Korea and Republic of Korea is a factor that may could also be represented simply as “hongjingtian” (红景天, support transboundary conservation and landscape level R. rosea), due to some authorities treating it as a synonym, management measures. Where R. sachalinensis occurs in the raw material (if exported) could be lumped in with other the northern Baekdudaegan Mountain Range,[24] there are Rhodiola species raw materials under the general HS Code nationally protected areas such as national parks, provincial 1211.90 (other plants and parts of plants, of a kind used parks, and natural forests covering 3035 km2. 63.4% is state primarily in pharmacy). It is also conceivable that exports land, 1.9% is public land, and 34.7% is privately owned. of extracts made from this species would be lumped in with A study has been carried out, aiming toward a collaborative other Rhodiola species extracts under the general HS Code strategy between China, DPR Korea, and Republic of Korea 1302.19 (other vegetable saps and extracts). No evidence of for an environmental protection management plan in the Mount illegal trade of R. sachalinensis was found. Paektu and Tuman River area, where R. sachalinensis is listed as a protected species on the China side. The Tuman River Management measures and cultivation forms a part of the international boundary between China, National legal instruments DPR Korea, and Russian Federation.[55] The “Regulations of the People’s Republic of China on Wild In the Russian Federation, R. sachalinensis is protected within Plants Protection”[51] have been in effect since 1997 and the state cadaster of specially protected natural areas (SPNAs) of cover all activities concerning the protection, development, regional significance in the Sakhalin Region.[56] R. sachalinensis and utilization of wild plants. The regulation references a also shares habitat with Rhodiola ishidae Hara, within an SPNA national list of wild plants under special state protection that of federal significance, Kurilsky State Nature Reserve.[57] The is periodically updated by the government. A new list was in reserve area is 65,861.5 ha (0.75% of the Sakhalin Oblast) preparation in 2020. It is anticipated that several species of and consists of three clusters: Two on , Rhodiola will be placed under second class protection, which Tyatinsky (northern), and Alekhinsky (southern), and one would make issuance of a collection permit compulsory. In on the , which includes Shikotan Island, 2017, the conservation status of R. sachalinensis was assessed where R. sachalinensis reportedly occurs.[58] On Sakhalin as Vulnerable (VU B1ab [i, iii]; D1) [Table 1].[7] Island, R. sachalinensis occurs in two regionally significant Management measures and challenges protected areas, Makarovsky Reserve and Izubrovy Reserve, Habitat conservation although these may be difficult to manage in consideration of [31] R. sachalinensis occurs in several protected areas. The the oil and gas pipelines. species is listed as a key protected plant species occurring in Cultivation and propagation the Ecologically Critical Area of broad‑leaved Korean R. sachalinensis is cultivated as a field crop in Jilin, China.[59] [22] mixed forest in the CMNR. The occurrence of this species Of the Rhodiola species cultivated in China, R. sachalinensis within the CMNR, which is also internationally recognized and R. angusta reportedly comprise the largest planting as a United Nations Educational, Scientific and Cultural area.[5] Cultivation is challenging, however. First, due to low Organisation Biosphere Reserve, are positive factors with salidroside levels in cultivated plants (0.1%–0.5%) compared regard to management. So is the fact that in 1986, the CMNR to wild populations on Changbai Mountain (0.5%–1.5%), and was officially recognized as a national‑level nature reserve second, due to root rot[60] and leaf wilt[59] in cultivated material. emphasizing forest protection.[42] R. sachalinensis is included From 2007 to 2011, 75%–95% of fields with cultivated on the list of wild plants under Jilin provincial protection in the R. sachalinensis in Siping District were affected by root rot CMNR for two reasons: It is (1) used in medicine (economic caused by Fusarium verticillioides.[60] The effect of root rot value); and (2) an alpine tundra seed plant, rare in quantity.[52] gets worse where R. sachalinensis plants are grown at a high In 2000, the Changbai Mountain Academy of Sciences, Erdao density, requiring the use of different antibacterial chemical Baihe Town Antu County, Jilin, began ex situ conservation treatments.[61] A South Korean patent was granted for methods of R. sachalinensis at the academy, which is within the to cultivate R. sachalinensis as a 4‑year field crop, at a lower CMNR. Seeds and seedlings were transplanted into an ex situ altitude range (700–1000 m a. s. l.), claiming to yield larger conservation area, situated only tens of kilometers from the roots than those of wild populations at their higher altitude main range of distribution of wild R. sachalinensis, sharing habitat.[23] A Chinese patent was also granted for the invention similar climatic conditions. About 500 individuals survived in of domesticating wild R. sachalinensis at an altitude of 800 m the ex situ conservation site.[1] What could further strengthen a. s. l.[62] Other Chinese patents have been granted for new these management measures is the recommendation by methods of breeding[63] and for cultivation of an improved Tang et al.[53] for multiscale, multistakeholder conservation variety of R. sachalinensis in a low‑altitude plain area, claiming efforts in the Changbai/Paektu mountain range. Forming the to solve the problems of poor seed germination, root rot,

World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 303 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

and low yield.[64] Growing R. sachalinensis as a shade crop being implicated. A particular case is R. sachalinensis, a using colored polyethylene shade has shown positive effects species that has a similar composition to R. rosea, containing on the accumulation of bioactive compounds. While the use rosavins (the marker compounds used to identify R. rosea), as of red film slightly decreased root biomass of 3–4‑year‑old well as salidroside, and is considered by some botanists to be R. sachalinensis, it significantly increased salidroside the same species as R. rosea. To complicate matters, different content.[65] However, the use of yellow, blue, and/or green populations of R. sachalinensis may display differences in polyethylene shade significantly decreased the salidroside their HPLC‑ultraviolet detection (UV) fingerprints, making content of the roots.[66] A study aiming to acquire homozygous accurate species identification based on chemical analysis tetraploid germplasm of R. sachalinensis resulted in providing difficult. However, substitution with R. sachalinensis may a scientific basis for polyploid breeding.[67] In northwestern become less of a concern, since its growing range has Sichuan, 280,000 R. sachalinensis seedlings were also decreased significantly and it is now considered to be critically transplanted as a part of a desertification control demonstration endangered in China.” On the other hand, R. sachalinensis project, with a reported survival rate of 40%–50%, according is also traded explicitly and therefore it is also possible to Chengdu Tiandi Net Information Technology Ltd.[10] that R. sachalinensis products could be adulterated or mixed with other Rhodiola species themselves. DNA Regarding experimental artificial propagation, in vitro barcoding and chemical methods could help to differentiate cultures have been obtained from the stems and leaves, Rhodiola species in such cases. For example, Wang and the latter proving to be best suited for shoot induction.[68] Guo used rapid static headspace‑gas chromatography–mass Biotechnological methods are also being explored to produce spectrometry to effectively differentiate the rhizomes of the pharmacological active compound salidroside at higher R. sachalinensis from those of another medicinal Rhodiola levels to wild or cultivated plants. In R. sachalinensis cell species, “shengdihongjingtian” (圣地红景天, Rhodiola suspension cultures, the salidroside content was ten times sacra (Prain ex Raym.‑Hamet) S. H. Fu).[71] Other methods higher than in wild‑collected plants. This finding could lead have been developed that distinguish R. sachalinensis samples to a preference for biotechnological production over obtaining from other Rhodiola species including R. rosea, using active compounds from field cultivated or wild‑collected nuclear magnetic resonance spectroscopy, metabolomics, and R. sachalinensis.[14] A study that analyzed genetic and epigenetic HPTLC,[11] as well as HPLC‑DAD/UV followed by principal differentiation in different populations of R. sachalinensis component analysis and nuclear magnetic resonance (HCA).[12] including three natural populations and an ex situ population found that that the ex situ population possessed significantly different genetic and epigenetic population structures and Conclusions HPLC fingerprint patterns. The researchers suggest that the While R. sachalinensis is increasingly produced by cultivation, ex situ environmental factors caused by different altitudes may wild populations are small, VU and decreasing due to multiple play an important role in keeping hereditary characteristics of threats. These include anthropogenic factors such as (a) R. sachalinensis ex situ populations.[1] habitat loss due to oil and gas infrastructure development, (b) Adulteration and substitution climate change impacts on alpine ecosystems, and (c) overexploitation of wild plants to satisfy the growing demand First, the 2019 Jilin Provincial Standards for Chinese for any Rhodiola species that are used interchangeably. Yet, Medicinal Materials provide a detailed monograph for only China has published an assessment of its conservation R. sachalinensis root and rhizome with four methods of status. Our findings suggest that resource assessments should identification (macroscopic, microscopic, TLC, and HPLC) be carried out and that monitoring of harvesting and trade of to verify botanical identity.[16] Compendial monographs such wild R. sachalinensis should commence in all countries where as the Jilin Provincial Standards require a combination of remaining populations exist, in order to facilitate sustainable techniques (orthogonal testing) due to the fact that a single exploitation. Furthermore, whether the raw material supply identification method does not offer a certainty of 100% is obtained from farm operations or from wild populations, confidence. The material must conform to all four identification we propose there is a need to implement credible voluntary tests. Second, the Herbal Medicines Compendium of the sustainability standards with independent third‑party United States Pharmacopoeia lists R. sachalinensis as a inspection and certification. Even with increasing reliance on potential confounding material in the supply of official cultivation, biodiversity conservation, and genetic diversity in R. crenulata.[69] Admixture or substitution with other similar wild populations are relevant for the future of TCM. looking Rhodiola species is known to occur in trade. Based largely on data from Booker et al.,[11] the Botanical Adulterants Acknowledgment Bulletin of the American Botanical Council, American Herbal This paper has been prepared in the course of a project Pharmacopoeia, and the University of Mississippi’s National funded by the German Ministry of the Environment, Nature Center for Natural Products Research[70] make this statement: Conservation and Nuclear Safety (BMU) and managed by “Although substitution of R. rosea products with R. crenulata the Federal Agency for Nature Conservation (BfN) (FKZ is considered the main problem with respect to authenticity 3519532056) that enabled us to assess the conservation of R. rosea, field work data suggest that other species are and trade issues facing R. sachalinensis. We would like to

304 World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

thank Honglin Li (Chengdu Institute of Biology) for her medicinal plants from the Qinghai-Tibetan Plateau. PLoS One help in obtaining some key references in Chinese and for 2015;10:e0119921. 14. Grech-Baran M, Sykłowska-Baranek K, Pietrosiuk A. Biotechnological searching for internet‑based trade in R. sachalinensis in China. approaches to enhance salidroside, rosin and its derivatives Dr Ben Legler (Collections Manager, Stillinger Herbarium, production in selected Rhodiola spp. in vitro cultures. Phytochem Rev University of Idaho) is thanked for his rapid response with 2015;14:657-74. regard to the R. sachalinensis specimen, he collected on 15. Li X, Nakamura S, Matsuda H, Yoshikawa M. Bioactive constituents from Chinese natural medicines. XXIX. Monoterpene and monoterpene Sakhalin Island. Expert advice that contributed to this work was glycosides from the roots of Rhodiola sachalinensis. Chem Pharm also received from Dr. Uwe Schippmann, former head of the Bull (Tokyo) 2008;56:612-5. Plant Conservation Division of BfN. We also thank Dr. Daniel 16. Jilin Provincial Drug Administration. Standards for Chinese Medicinal (BfN) for his review and comments on the final draft. Materials of Jilin Province. Vol. 1. : Jilin Science and Technology Press; 2019. (in Chinese). Financial support and sponsorship 17. Zhejiang Provincial Drug Administration. Standards for Chinese Materials of Zhejiang Province. Vol. 1. Hangzhou: Zhejiang Medical Nil. Products Administration; 2017. (in Chinese). Conflicts of interest 18. Komarov VA, Yuzepchuk SV, editors. Flora of the U.S.S.R. (Flora SSSR), Volume IX. Rosales and Sarraceniales. Moscow and Leningrad: Prof. Josef A. Brinckmann is an editorial Board member of Botanical Institute of the Academy of Sciences of the U.S.S.R; 1939. World Journal of Traditional Chinese Medicine. The article p. 26, 359-60. was subject to the journal's standard procedures, with peer 19. Fu SG, Li YQ, Wang CM. Chinese Patent: CN103875431B. Beijing: China National Intellectual Property Administration; 2015. (in Chinese). review handled independently of this editorial board member 20. Liu JF, Cheng YQ, Yang J. Conservation of in vitro shoots of Rhodiola and their research groups. sachalinensis by slow growth and genetic stability of recovered plantlets. J Biotechnol 2008;136S: S154. 21. Fan W, Tezuka Y, Ni KM, Kadota S. Prolyl endopeptidase inhibitors References from the underground part of Rhodiola sachalinensis. Chem Pharm 1. Zhao W, Shi X, Li J, Guo W, Liu C, Chen X. Genetic, epigenetic, and Bull (Tokyo) 2001;49:396-401. HPLC fingerprint differentiation between natural and ex situ populations 22. Yu LQ, Li JW, Zhao XH, Ma L, Wu S, Bai XQ. Ecologically critical of Rhodiola sachalinensis from Changbai Mountain, China. PLoS One areas of broad-leaved Korean pine mixed forest in Changbai Mountains, 2014;9:e112869. China. Chin J Appl Ecol 2014;25:1250-8. 2. Fu F, Ohba H, Gilbert MG. Crassulaceae Candolle. In: Wu ZY, Raven PH, 23. Jang HS. A Method for Growing Rhodiola sachalinensis A. Bor. editors. Flora of China. (Brassicaceae through Saxifragaceae). Vol. 8. Publication No. 10-2007-0115155. : Korea Intellectual Beijing, and Missouri Botanical Garden Press, St. Louis: Science Press; Property Office, Daejeon; 2007. (in Korean). 2001. p. 251‑68. 24. Kim DW, Kim JH, Kim KH, Jin MH, Son SK Lee JR, et al. Cosmetic 3. Li T, Xu G, Wu L, Sun C. Pharmacological studies on the sedative Composition for Hair Strengthening. Geneva: World Intellectual and hypnotic effect of salidroside from the Chinese medicinal plant Property Organization; 2016. Rhodiola sachalinensis. Phytomedicine 2007;14:601‑4. 25. Sundukov Y, Sundukov L. Plant world of Shikotan Island. Kurilsky 4. Song J, Wu Y, Jiang G, Feng L, Wang Z, Yuan G, Tong H. Sulfated Nature Reserve (in Russian). Available from: http://kurilskiy.ru/. [Last polysaccharides from Rhodiola sachalinensis reduce d‑gal‑induced accessed on 2021 July 13]. oxidative stress in NIH 3T3 cells. Int J Biol Macromol 2019;140:288‑93. 26. Probatova NS, Barkalov VY, Rudyka EG, Pavlova NS. Further 5. Cui JL, Guo TT, Ren ZX, Zhang NS, Wang ML. Diversity and chromosome studies on vascular plant species from Sakhalin, Moneran antioxidant activity of culturable endophytic fungi from alpine plants and Kurile Islands. Bull Hokkaido Univ Mus 2006;2:93-110. of Rhodiola crenulata, R. angusta, and R. sachalinensis. PloS One 27. Gage S, Joneson SL, Barkalov VY, Eremenko NA, Takahashi H. 2015;10:e0118204. A newly compiled checklist of the vascular plants of the Habomais, the 6. Ministry of Environmental Protection and Chinese Academy of Little Kurils. Bull Hokkaido Univ Mus 2006;3:67-91. Sciences. China’s Red List of Biodiversity-Higher Plant Volume. 28. Gontcharova SB, Gontcharov AA, Yakubov VV, Kondo K. Seed surface Ministry of Ecology and Environment of the People’s Republic of morphology in some representatives of the Genus Rhodiola sect. China, Beijing (in Chinese) 2013. Available from: http://www.mee. Rhodiola (Crassulaceae) in the Russian Far East. Flora 2009;204:17-24. gov.cn/gkml/hbb/bgg/201309/W020130917614244055331.pdf. [Last 29. Pietsch TW, Bogatov VV, Storozhenko SY, Lelej AS, Barkalov, VY, accessed on 2021 July 13]. Takahashi H, et al. Biodiversity and biogeography of Sakhalin Island. 7. Qin H, Yang Y, Dong S, He Q, Jia Y, Zhao L, et al. Threatened species In: Storozhenko SY, Bogatov VV, Lelej AS, Makarchenko EA, editors. list of China’s higher plants. Biodiv Sci 2017;25:696-744. Flora and Fauna of North-West Pacific Islands (Materials of International 8. The Plant List, Version 1.1, 2013. Available from: http://www. Kuril Island and International Sakhalin Island Projects). Vladivostok, theplantlist.org/.[Last accessed on 2021 July 13]. Russian Federation: Publishing House Dalnauka; 2012. p. 11-78. 9. International Crassulaceae Network. Available from: https://www. 30. Yan TF, Zu YG, Yan XF, Zhou FJ. Genetic structure of endangered crassulaceae.ch/de/home.[Last accessed on 2021 July 13]. Rhodiola sachalinensis. Conserv Genet 2003;4:213-8. 10. Cunningham AB, Li H, Luo P, Zhao WJ, Long XC, Brinckmann JA. 31. Sakhalin Energy Investment Company (SEIC). EIA addendum: There “ain’t no mountain high enough”? The drivers, diversity and Chapter 11 – Protected areas. In: Executive Summary of the Phase 2 sustainability of China’s Rhodiola trade. J Ethnopharmacol 2020;252. Environmental and Social Impact Assessment Process. Sakhalin II https://doi.org/10.1016/j.jep.2019.112379. Phase 2 Project. Russian Federation: SEIC, Yuzhno-Sakhalinsk; 2005. 11. Booker A, Zhai L, Gkouva C, Li S, Heinrich M. From traditional 32. Zhu L, Li Z, Zhang Y, Wang X. A 211-year growing season temperature resource to global commodities: A comparison of Rhodiola species using reconstruction using tree-ring width in Zhangguangcai Mountains, NMR spectroscopy – Metabolomics and HPTLC. Front Pharmacol Northeast China: Linkages to the pacific and Atlantic oceans. Int J 2016;7:254. Climatol 2017;37:3145-53. 12. Liu Z, Liu Y, Liu C, Song Z, Li Q, Zha Q, et al. The chemotaxonomic 33. IUCN Standards and Petitions Committee. Guidelines for Using the classification of Rhodiola plants and its correlation with morphological IUCN Red List Categories and Criteria. Version 14. Prepared by the characteristics and genetic taxonomy. Chem Cent J 2013;7:118-26. Standards and Petitions Committee; 2019. Available from: http://www. 13. Zhang JQ, Meng SY, Wen J, Rao GY. DNA barcoding of iucnredlist.org/documents/RedListGuidelines.pdf. [Last accessed on Rhodiola (crassulaceae): A case study on a group of recently diversified 2021 July 13].

World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021 305 [Downloaded free from http://www.wjtcm.net on Wednesday, September 1, 2021, IP: 10.232.74.26]

Brinckmann, et al. Reviewing threats to wild Rhodiola sachalinensis

34. Biodiversity Center of Japan and Japanese Ministry of Environment. on Changbai Mountain, China, and (DPRK). Mt Res Dev Red List 2020. Vascular plants (in Japanese). Available from: https:// 2011;31:169-75. ikilog.biodic.go.jp/Rdb/booklist.[Last accessed on 2021 July 13]. 54. Kong WS. Ecological issues and prospects on the Korean peninsula. 35. Kang CG, Pak GJ, Kim YB, editors. Red Data Book of DPR In: International Conference for Ecozoic Culture 2018 Ecological Korea (Plants). , DPR Korea: MAB National Committee Transformation on the Korean Peninsula and in East Asia, October 12th- of DPR Korea, Botanical Institute, Biological Branch, Academy of 14th, 2018. Hotel Jijihyang, Paju Book City, GyeongGi-Do, South Korea: Sciences; 2005. Institute for Ecological Civilization, San Diego, California; 2018. 36. Kamelin RV, Novikov VS, editors. Red Book of the Russian Federation p. 387-404. (Plants and Fungi). Moscow: KMK Scientific Press, Ltd.,; 2008. p. 182- 55. Kang TG. A Study on Development and Environmental Status along the 3. (in Russian). Borders between North Korea and China. Sejong: Korean Environment 37. Institute of Biology and Soil Science, Russian Academy of Sciences Institute; 2013. Far-Eastern Branch. Red Data Book of Primorsky Krai. Plants: Rare and 56. Ministry of Forestry and Hunting. State Cadastre of Specially Protected Endangered Species of Plants and Fungi. Vladivostok: Administration Natural Territories of Regional Value, Sakhalin Region. Yuzhno- of Primorsky Krai; 2008. (in Russian). Sakhalinsk, Sakhalin Island: Ministry of Forestry and Hunting Sakhalin 38. Eremin EV, Taran AA, editors. Red Data Book of Sakhalin Region. Oblast; 2017. (in Russian). Plants and Fungi. Kemerovo: Technoprint LLC; 2019. (In Russian). 57. Ministry of Natural Resources of the Russian Federation. Cadastral 39. Graybill JK. Mapping an emotional topography of an ecological information about FSBI (Federal State Budgetary Institution) “Kurilsky homeland: The case of Sakhalin Island, Russia. Emot Space Soc State Reserve” (for the period 2009-2014). Yuzhno-Kurilsk, Sakhalin 2013;8:39-50. Region: Ministry of Natural Resources of the Russian Federation; 2015. 40. Mikhailovskaya LN, Molchanova IV, Pozolotina VN, Zhuravlev YN, (in Russian). Timofeeva YO, Burdukovsky ML. Radioactive contamination of the 58. Kurilsky Nature Reserve; 2011-2021. Available from: http://www. soil-plant cover at certain locations of Primorsky Krai, Sakhalin Island kurilskiy.ru/?territory,kurilskiy. [Last accessed on 2021 July 13]. and Kamchatka Peninsula: Assessment of the Fukushima fallout. 59. Bai Q, Xie Y, Wang X, Li Y, Gao J, Li J, et al. First report of damping-off J Environ Radioact 2017;172:1-9. of Rhodiola sachalinensis caused by Rhizoctonia solani AG-4 HG-II in 41. Zhang J, Liu F, Cui G. The efficacy of landscape-level conservation China. Plant Dis 2012;96:142. in Changbai Mountain Biosphere Reserve, China. PLoS One 60. Liu JF, Cheng YQ. First report of root rot on Rhodiola sachalinensis 2014;9:e95081. caused by Fusarium verticillioides (Gibberella fujikuroi) in China. Plant 42. Bai J, Tang L, Wang Q, Li F. A landscape-scale adjoining Dis 2011;95:222. conservation (LAC) approach for efficient habitat expansion: The case 61. Li XY, Quan CW, Huang SC, Shi TY. Studies on identifying pathogens of Changbai Mountain, Northeast China. Sustainability 2018;10:2919. of Rhodiola sachalinensis damping-off and on its medicamental 43. Ma L, Sun GQ, Qu Y, Li JQ. Applying systematic conservation planning prevention and cure. J Jilin Agric Univ 2002;24:112-4. to constitute a protection strategy for broad-leaved Korean pine forests 62. Jiang YJ, Li RL, Lin X, Guo D, Yuan ZJ, Wang SL. Artificial Cultivation in Changbai Mountains, China. J Mt Sci 2016;13:493-507. Method for Wild Rhodiola Sachalinensis. Beijing: China National 44. You J, Qin X, Ranjitkar S, Lougheed SC, Wang M, Zhou W, et al. Intellectual Property Administration; 2011. Response to climate change of montane herbaceous plants in the genus 63. Fu SG, Li YQ, Wang CM. Chinese Patent: CN103875431B. Beijing: Rhodiola predicted by ecological niche modelling. Sci Rep 2018;8:5879. 45. Jiang ML, Zhong WT, Han H. Studies on producing effective medicinal China National Intellectual Property Administration; 2015. ingredients of Rhodiola sachalinensis by tissue culture. J Shenyang 64. Fu SG, Li YQ, Wang CM. Chinese Patent: CN103875431A. Beijing: Agric Univ 1994;25:355-9. China National Intellectual Property Administration; 2014. 46. Yan X, Wu S, Wang Y, Shang X, Dai S. Soil nutrient factors related to 65. Yan X, Wang Y, Guo S, Shang X. Seasonal variations in biomass salidroside production of Rhodiola sachalinensis distributed in Chang and salidroside content in roots of Rhodiola sachalinensis as affected Bai Mountain. Environ Exp Bot 2004;52:267-76. by gauze and red film shading. Chin J Appl Ecol 2004;15:382-6. (in 47. Cuerrier A, Tendland Y, Rapinski M. Ethnobotany and conservation of Chinese). Rhodiola species. In: Cuerrier A, Ampong-Nyarko K, editors. Rhodiola 66. Jin M, Zhu ZB, Guo QS, Shen HJ, Wang YR. Growth and accumulation rosea. Boca Raton, Florida: CRC Press; 2014. p. 35-63. of bioactive compounds in medicinal Chrysanthemum morifolium 48. Guo JP, Ding X, Guan QX. Rhodiola Sachalinensis Total Polyphenol Ramat. cv. ‘Chuju’ under different colored shade polyethylene. J Med Dispersible Tablets and Preparation Method and Application Thereof. Plants Res 2012;6:398-404. Beijing: China National Intellectual Property Administration; 2016. 67. Liu JF, Liu JH, Cheng YQ, Zhong X, Chen ZW. Acquiring homozygous 49. Gu ZB, Zhang J, Tao YH, Zeng C, Xu L. Method for Extracting tetraploid germplasm by PEG-mediated protoplast fusion of Rhodiola Herbacetin from Plants of Rhodiola L. United States Patent: 10,435,384. sachalinensis. China J Chin Mater Med 2010;35:1783-8. (in Chinese). Alexandria, Virginia: United States Patent and Trademark Office; 2019. 68. Liu HJ, Guo B, Yan Q, Liu YJ, Liu CZ. Tissue culture of four Rhodiola 50. Hu GA, Lao J, He W. A Soothing Body Milk Based on Root Extract species. Acta Bot Boreal Occident Sin 2006;26:2023-7. (in Chinese). of Rhodiola Sachalinensis and a Preparation Method Thereof. Beijing: 69. United States Pharmacopeial Convention. Rhodiola Crenulata Root China National Intellectual Property Administration; 2019. and Rhizome. Final Authorized. Ver. 1.0. Rockville, MD: United States 51. State Council of the People’s Republic of China, Regulations of the Pharmacopoeial Convention; 2016. People’s Republic of China on Wild Plants Protection; 1996. Available 70. Bejar E, Upton R, Cardellina 2nd JH. Adulteration of Rhodiola (Rhodiola at: http://www.fao.org/faolex/results/details/en/c/LEX-FAOC012060. Rosea) Rhizome and Root and Extracts. Austin, Texas: ABC-AHP- [Last accessed on 2021 Jul 14]. NCNPR Botanical Adulterants Bulletin; 2017. 52. Changbai Mountain Academy of Sciences. Impacts and Countermeasures 71. Wang HY, Guo YL. Rapid analysis of the volatile compounds in the of Global Climate Changes on Alpine Areas. Erdaobaihe Town, Jilin: rhizomes of Rhodiola sachalinensis and Rhodiola sacra by static UNESCO; 2009. headspace-gas chromatography-tandem mass spectrometry. Anal Lett 53. Tang L, Li A, Shao G. Landscape-level forest ecosystem conservation 2004;37:2151-61.

306 World J Tradit Chin Med | Volume 7 | Issue 3 | July-September 2021