Vid de seda china

Chinese Silkvine (Periploca sepium Bunge): A Comprehensive Reference

1. Identity and Botanical Description

1.1 Taxonomic Classification and Nomenclature

Chinese silkvine is the common English name for Periploca sepium Bunge, a member of the family Apocynaceae and the genus Periploca. The family classification has been variably cited in older literature — older taxonomic sources also placed it within the family Asclepiadaceae, now considered a subfamily of Apocynaceae. The genus name derives from Greek, referring to the twining habit of these vines. The species epithet sepium relates to hedges, reflecting the plant's growth habit along thickets and margins.

Common names include "Chinese silk vine," "Chinese silkvine," and "spider vine." In Chinese, the root bark drug material is most widely known as Xiangjiapi (香加皮) or Bei-wujiapi (北五加皮). In German it is known as chinesische Baumschlinge. The medicinal drug material — the dried root bark — is called Cortex Periplocae in pharmacopoeial Latin.

The genus Periploca is broadly distributed: it comprises approximately 17 species distributed across temperate Asia, southern Europe, and tropical Africa. Most plants in this genus exhibit significant medicinal value.

1.2 Botanical Morphology

Periploca sepium is a perennial climbing plant native to regions of East Asia, including China, Japan, and Korea, and is often found in temperate regions. It is a deciduous vine that can climb to considerable heights, often reaching up to 10 meters (about 30 feet). The leaves are glossy, dark green, and typically arranged in opposite pairs; they can be lanceolate to elliptical in shape, measuring around 5 to 10 cm in length and 2 to 4 cm in width, with smooth margins.

The flowers are dark purple outside and greenish inside, ill-scented, and star-shaped. Following the flowering period, the plant develops elongated, cylindrical seed pods that can reach lengths of about 10 to 15 cm and contain flat, winged seeds dispersed by wind. Like the Para-rubber tree (Hevea brasiliensis), Periploca produces a milky exudate containing rubber latex.

1.3 Geographical Origin and Distribution in China

Cortex Periplocae (Xiangjiapi) is primarily distributed across the Northern, Northeastern, and Northwestern regions of China, according to the Chinese Pharmacopoeia Commission (2025). The plant originally comes from Northwest China. The root bark is typically harvested in spring or autumn and is the basis of a common Chinese herbal medicine with outstanding attributed efficacy.

1.4 Common Forms and Preparations

The primary medicinal form is the dried root bark (Cortex Periplocae). The processing of Cortex Periplocae requires removing impurities, cleaning, slicing, and drying; the dried cortex (3–6 g) and other medicinal materials are typically decocted in water and taken for internal use. In research contexts, aqueous extracts, alcohol (butanol) extracts, and purified fractions — particularly the cardiac glycoside-free pregnane glycoside fraction known as periplosides (PePs) — have been employed. Individual purified compounds such as periplocin, periplocymarin, and specific periplocosides have also been studied in isolation.

2. Traditional and Historical Use

2.1 Traditional Chinese Medicine (TCM)

The root bark of P. sepium, known as "Xiangjiapi" or "Bei-wujiapi," is utilized as a traditional Chinese medicine for the treatment of rheumatoid arthritis and bone and muscle pain, and is recorded in the Chinese Pharmacopoeia (2015 version). The root of P. sepium is commonly used in traditional Chinese medicine as "Xiangjia Pi," which has diuretic effects, dispels edema, alleviates rheumatism, and strengthens muscles and bones.

Historically, Chinese silkvine was incorporated into herbal formulations to treat conditions such as rheumatism, edema, and urinary difficulties; its use is documented in classical TCM texts, where it was valued for its purported ability to dispel wind and dampness, clear heat, and promote the flow of qi. The Chinese Pharmacopoeia Commission recognizes its outstanding attributed efficacy in removing edema, expelling wind-damp, and strengthening the bones and muscles, with clinical use directed at relieving rheumatic conditions, reducing dropsy, and treating cardiovascular disease.

Cortex Periplocae is a famous and commonly used traditional Chinese medicine with a long history in China, often used for the clinical treatment of rheumatoid arthritis and chronic congestive heart failure.

2.2 Recognition of Traditional Toxicity

Historical Chinese medical literature acknowledged the plant's risks. The historical text Sichuanzhongyaozhi labeled it as "toxic, not appropriate to use for long time," demonstrating that people long ago recognized the toxicity of Cortex Periplocae. The dual nature of Chinese silkvine — therapeutic in appropriate doses, dangerous in excess — has therefore been recognized for centuries within the TCM tradition.

2.3 Nomenclatural Note: Confusion with Related Herbs

A historically significant issue involves the confusion of Xiangjiapi (P. sepium) with Wu Jia Pi, a name that also refers to root barks of Eleutherococcus species. Adulteration of eleuthero root with related species from the genus Eleutherococcus, as well as Periploca sepium (Chinese silk vine), has been documented in the medicinal plant literature. This confusion has had documented consequences (see Safety section below).

3. Key Constituents and Active Compounds

3.1 Overall Chemical Profile

More than 100 constituents have been isolated and identified from Cortex Periplocae, including steroids, cardiac glycosides, terpenoids, and fatty acid compounds. These species are well-known to be rich sources of diverse and complex natural products — above all, cardiac steroids and C21 pregnane steroids with special structures and obvious pharmacological activities; the various crude extracts and 314 isolated metabolites from the genus have attracted much attention in intensive biological studies, indicating that they are equipped with cardiotonic, anti-inflammatory, immunosuppressive, antitumor, antimicrobial, antioxidant, insecticidal and other properties.

3.2 Cardiac Glycosides

The cardiac glycoside fraction is pharmacologically the most studied. The principal cardiac glycosides from P. sepium root bark include periplocin, periplocymarin, and periplogenin, among others. The principal active constituent is periplocin (C₃₆H₅₆O₁₃), a major cardiac glycoside that has been widely documented to possess significant cardiotonic, antitumor, and anti-rheumatic effects.

Isolated cardiac glycosides from the root bark include periplocin, glucosyl divostroside, periplogenin, periplocymarin, and periplocoside M, with periplocin exhibiting the lowest IC50 value against leukemia and liposarcoma cells in cytotoxicity screening.

Periplocin is a plant-derived glycoside in which the sugar moiety is linked to a steroid; it was first reported in 1897 from the stem bark of Periploca graeca from the southwest Caucasus in the Black Sea region, and can also be extracted from Periploca calophylla, Periploca forrestii, Periploca omeiensis, and the traditional Chinese medicine Cortex Periplocae (the dry root bark of Periploca sepium).

3.3 Pregnane Glycosides (C21 Steroidal Glycosides)

The pregnane glycoside fraction — also called "periplosides" (PePs) — is structurally distinct from the cardiac glycoside fraction and has been the subject of intensive immunopharmacological research. The periplosides (PePs), isolated from the root bark of P. sepium and characterized as the cardiac glycoside-free pregnane glycoside fraction, are expected to possess therapeutic potential on inflammatory arthritis. Named compounds include periplocoside A, periplocoside E, and a series of additional periplocosides (B, C, D, F, J, K, L, M, O, and others).

Nine pregnane glycosides containing peroxy functions in their sugar moieties, five oligosaccharides, six additional pregnane glycosides, and five cardiac glycosides have been isolated from the root barks of Periploca sepium.

3.4 Aromatic and Volatile Compounds

Periploca species are rich in aromatic compounds and volatile oils, especially P. sepium; only 4-methoxysalicylaldehyde is assigned as the index component for the quality evaluation of P. sepium root bark in the Chinese Pharmacopoeia (2015 Version), which requires its content to be not less than 0.20%. The compound 2-hydroxy-4-methoxybenzaldehyde (also called 4-methoxysalicylaldehyde) is a phenolic aldehyde characteristic of the root bark essential oil and serves as the official quality-control marker.

4. Mechanisms of Action

4.1 Na+/K+-ATPase Inhibition (Cardiac Glycoside Mechanism)

Periplocymarin has a strong cardiac glycoside structure with a strong affinity for Na+/K+-ATPase, which inhibits Na+/K+-ATPase activity by binding to Na+/K+-ATPase in the myocardial cell membrane, leading to increased Ca2+ inward flow, increased intracellular Ca2+ concentrations in the myocardium, and enhanced myocardial contractility, similar to the effects of digoxin. Periplocin can selectively act on the heart to strengthen positive muscle strength by increasing myocardial contractility and slowing down the heart rate.

4.2 Immunosuppression via T-Cell Inhibition

The most potent immunosuppressive compound identified from P. sepium, periplocoside E (PSE), a pregnane glycoside, was isolated via bioactivity-guided fractionation. Investigation of its immunosuppressive effects showed that PSE in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A and mixed lymphocyte culture reaction at non-cytotoxic concentrations (<5 μM), and administration of PSE suppressed a delayed-type hypersensitivity reaction and ovalbumin-induced antigen-specific immune responses in mice.

4.3 NF-κB Pathway Inhibition

Periplocin treatment decreased cell viability and cytokine expression and promoted cell apoptosis of TNF-α-induced rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) through inhibition of the NF-κB signaling pathway. Cell viability of TNF-α-induced RA-FLSs was inhibited in a dose-response manner by periplocin, while cell apoptosis of RA-FLSs was triggered by a dose-dependent effect; Bcl-2 protein was downregulated, while BAX, cleaved caspase-3, and cleaved caspase-9 were upregulated in RA-FLSs under periplocin treatment.

4.4 Anticancer Apoptotic Pathways

Cardiac glycosides (CGs) are candidate anticancer agents that function by increasing intracellular Ca2+ to induce apoptotic cell death in several types of cancer cells; new findings have shown that the anti-cancer effects of CGs involve complex cell-signal transduction mechanisms. Multiple signaling pathways have been implicated in periplocin's anti-cancer action, including the β-catenin/TCF pathway, the ERK1/2-EGR1 pathway, the AMPK/mTOR pathway, and death receptor-mediated pathways.

4.5 Macrophage Polarization Modulation

Cortex Periplocae has been widely employed in traditional Chinese medicine to alleviate rheumatoid arthritis and harbors a bioactive compound known as Periploca sepium periplosides (PePs). Recent preclinical research indicates that PePs effectively attenuated collagen antibody-induced arthritis (CAIA) by suppressing the polarization of macrophages towards the M1 phenotype while promoting an alternative polarization state — a mechanism relevant to the modulation of synovial inflammation in rheumatoid arthritis.

5. Scientific Evidence by Area of Use

5.1 Rheumatoid Arthritis and Anti-Inflammatory Activity

This is the area with the greatest concentration of published research, though the evidence remains predominantly preclinical (animal and cell-based). There are no published randomized controlled clinical trials (RCTs) in humans identified from the available scientific literature.

Cell-based evidence: Periploca sepium has traditionally been used in oriental medicine for treatment of rheumatoid arthritis (RA). Investigation of the aqueous extract of P. sepium on human rheumatoid arthritis-derived fibroblast-like cells showed that the extract inhibited the growth and IL-6 production of the cells in dose-dependent manners. Study of extract fractionation indicated that the active material inhibiting IL-6 production is filterable by ultrafiltration, suggesting that substances with low molecular weight might be involved in an inhibition of IL-6 production.

Animal study evidence: Periploca sepium is used in TCM for the treatment of autoimmune diseases, particularly rheumatoid arthritis; in-vivo results justified the traditional use of Periploca sepium for the treatment of diseases associated with inflammation and pain. In the collagen antibody-induced arthritis (CAIA) mouse model, treatment with PePs was evaluated by measuring paw thickness, clinical arthritis scores, and histological changes in joint tissues.

Evidence strength: Anti-inflammatory and anti-arthritic evidence is currently limited to cell culture and rodent models. No human clinical trial evidence is available, and this area is best characterized as preliminary.

5.2 Cardiotonic Activity

Periplocymarin, which belongs to the cardiac glycosides, is an effective component extracted from Periplocae Cortex; its cardiovascular effects were studied by injection of periplocymarin (5 mg/kg) through the external jugular vein, which immediately increased mean arterial pressure (MAP) in anesthetized C57BL/6 mice. Echocardiography was used to evaluate the effects on cardiac function; results showed that injection of periplocymarin significantly increased the ejection fraction (EF) in mice without changing the heart rate.

Periplocin undergoes hydrolysis and deglycosylation to yield periplocymarin (PPM), which has a potent cardiotonic effect in vivo. The traditional application of Cortex Periplocae in congestive heart failure is supported biologically by this Na+/K+-ATPase inhibition mechanism. However, as with the anti-inflammatory evidence, no published human RCT data are available; the cardiotonic evidence base is pharmacological and animal-derived.

Evidence strength: Preclinical (animal and mechanistic). No human clinical trial data identified.

5.3 Anticancer Activity

Periplocin and periplocymarin have been studied in cell lines and animal tumor models across multiple cancer types. All published evidence is preclinical.

Colorectal cancer: Periplocin, a major bioactive component of the traditional Chinese herb Cortex Periplocae, has been reported to be a potential anticancer drug; it exhibits promising anticancer activity against colorectal cancer both in vitro and in vivo; mechanistically, periplocin promotes lysosomal damage and induces apoptosis in colorectal cancer cells.

Pancreatic cancer: Periplocin activates the β-catenin/TCF signaling pathway; in human colon cancer SW480 cells and nude mouse intraperitoneal tumor models, intraperitoneal administration of periplocin (30 mg/kg body weight/day) for 12 days inhibited colon cancer growth and induced apoptosis.

Liposarcoma: Liposarcomas are rare tumors within the heterogeneous group of soft tissue sarcomas and respond poorly to conventional treatments; periplocin led to growth inhibition and apoptosis induction by changing the expression of death receptors and inducing DNA double-strand breaks in SW-872 cells; periplocin displays a promising mechanism of action in sarcoma cells because altering the death receptor expression is an interesting target in sarcoma treatment, especially to overcome TRAIL resistance.

Gastric cancer: Periplocin can inhibit the proliferation of gastric cancer cells by inducing apoptosis in vitro and in vivo, and the ERK1/2-EGR1 pathway may mediate the cellular effects of periplocin; these findings provide an experimental basis for using periplocin as a chemotherapeutic drug against gastric cancer cells.

Colorectal cancer (periplocymarin): Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound; its effect on colorectal cancer cells has been explored. It has been found that PPM promoted prostate adenocarcinoma (PC3) cell apoptosis and inhibited proliferation of U937, HCT-8, Bel-7402, BGC823, A549, and A2780 cell lines in vitro with IC50 values of 0.02–0.29 mM.

Lung cancer: Multiple lines of evidence from recent investigation suggest that periplocin possesses anticancer activities against various types of cancers including colorectal cancer, esophageal carcinoma, pancreatic cancer, and liposarcoma; periplocin is a major cardiac glycoside found in Cortex Periplocae that was initially recognized in cardiovascular and autoimmune diseases, and inspired by recent findings its potential effects against lung cancer have also been investigated.

Evidence strength: All anticancer evidence for P. sepium compounds is in vitro and/or in vivo in animal xenograft models. No human oncology clinical trials have been published. Findings are early-stage and hypothesis-generating only.

5.4 Immunomodulatory Activity

Administration of periplocoside E (PSE) suppressed a delayed-type hypersensitivity reaction and ovalbumin-induced antigen-specific immune responses in mice; in vivo treatment with PSE dose-dependently suppressed OVA-induced proliferation and cytokine (IL-2 and IFN-γ) production from splenocytes.

Periplocoside A (PSA) has also been studied in autoimmune contexts. Examination of the protective effects of PSA on concanavalin A-induced hepatitis showed that pretreatment with PSA dramatically ameliorated concanavalin A-induced liver injury, characterized by reducing serum alanine transaminase (ALT), pathogenic cytokines of interleukin (IL)-4 and IFN-γ levels, impeding liver necrosis, and elevating the survival rate; in vitro, PSA inhibited IL-4 and IFN-γ productions of alpha-galactosylceramide-activated Natural Killer T (NKT) cells.

Oral administration of PSA significantly reduced the incidence and severity of experimental autoimmune encephalomyelitis (EAE), which closely paralleled the inhibition of MOG35–55-specific IL-17 production; Periploca sepium is a traditional Chinese herbal medicine used for treating rheumatoid arthritis in China.

Evidence strength: Immunomodulatory evidence is entirely preclinical (mouse models and cell culture). No human data available.

5.5 Antimicrobial, Antioxidant, and Other Activities

Using a bioassay-guided method, 2-hydroxy-4-methoxybenzaldehyde isolated from the root bark of Periploca sepium showed repellent activity against the olive weevil (Dyscerus perforatus) at various concentrations. Antimicrobial and antioxidant activities have also been documented for root bark essential oil and its main component, 2-hydroxy-4-methoxybenzaldehyde. These activities are relevant to agricultural and food-science applications but do not constitute clinical evidence for human health use.

6. Body Systems and Health Areas

Based on the available scientific literature, Chinese silkvine has been associated with research and traditional use in the following body systems:

• Musculoskeletal system: Rheumatoid arthritis, bone and joint pain, rheumatism, muscle weakness — the primary traditional and pharmacological focus.
• Cardiovascular system: Cardiotonic activity, chronic congestive heart failure, effects on myocardial contractility and heart rate via Na+/K+-ATPase inhibition.
• Immune system: T-cell suppression, macrophage polarization modulation, cytokine inhibition (IL-2, IL-6, IL-17, IFN-γ).
• Renal/urinary system: Diuretic effects, reduction of edema — traditional use well-documented.
• Oncology (experimental only): Apoptosis induction in colorectal, pancreatic, gastric, esophageal, lung, and sarcoma cell lines and xenograft models. No human cancer therapy application established.

7. Dosage Forms and Reported Dosages

7.1 Traditional / Pharmacopoeial Dosage

In the Chinese Pharmacopoeia, the dosage of "xiangjiapi" ranges from 3 g/60 kg/day to 6 g/60 kg/day. Processing requires removing impurities, cleaning, slicing, and drying; the dried Cortex Periplocae (3–6 g) and other medicinal materials are decocted in water and taken for internal use.

7.2 Dosages in Preclinical Studies

Dosages used in preclinical studies vary substantially by compound, route of administration, and model used, and are not directly applicable to human use:

• In human colon cancer SW480 cells and nude mouse intraperitoneal tumor models, intraperitoneal administration of periplocin at 30 mg/kg body weight per day for 12 days was used to inhibit colon cancer growth and induce apoptosis.
• In anesthetized C57BL/6 mice, injection of periplocymarin at 5 mg/kg through the external jugular vein immediately increased mean arterial pressure (MAP).
• Periplocoside E (PSE) significantly inhibited splenocyte proliferation at non-cytotoxic concentrations less than 5 μM in cell culture experiments.
• After a single oral administration of periplocin at 50 mg/kg to rats, periplocin could not be detected at any time point in plasma, while mean plasma profiles of its two metabolites periplocymarin and periplogenin were regular.

8. Safety Considerations

8.1 Official Toxicity Classification

The 2015 edition of the Pharmacopoeia of the People's Republic of China recorded Cortex Periplocae as toxic; the main toxic components are periplocin and its aglycone, which are classified as cardiac glycosides, and these toxic substances, used improperly, can easily trigger cardiotoxicity.

8.2 Cardiotoxicity

Periplocin enhanced the tonus and contractility of the cardiac muscle, as well as the tonus of the arterial muscle, whereas it led to cardiac irregularity and systolic arrest of the rat heart at excessive doses. At 0.39 mg/kg, periplocin brought about electrocardiogram abnormalities in half of the tested guinea pigs; the content of periplocin had a tight correlation with the acute toxicity test results of the water extract from the root bark of P. sepium.

Periplocin, the main substance in Periploca sepium Bunge, easily triggered cardiotoxicity because of improper application. Improper use of Cortex Periplocae often leads to cardiac toxicity, which in the most severe cases can even be life-threatening.

8.3 Hepatotoxicity

Some cardiac glycosides from the genus Periploca showed hepatotoxicity and cardiotoxicity at certain doses. All components, water extraction components, and alcohol extraction components of Cortex Periplocae showed acute toxicity in mice; through accumulative toxicity experiments, rats showed serious reactions under large dosages of Cortex Periplocae extraction.

8.4 Causes of Intoxication

Many conditions may cause intoxication, such as overdosage, drug confusion, incompatibility with herbs, and improper decoction, causing life-threatening complications; it is therefore necessary to normalize dosage and administration.

8.5 Pharmacokinetics and Mutagenicity

The oral bioavailability of periplocin in rats was found to be low. The tissue distributions of periplocin and two metabolites were found to include the heart, liver, spleen, lung, and kidneys, but a small amount of chemical constituents were distributed in the brain.

A mutagenicity study evaluated P. sepium root bark using the Ames test and chromosomal aberration tests. The root barks of Periploca sepium have been used in traditional Chinese medicine for healing wounds and treating rheumatoid arthritis; however, toxicity in high doses was often diagnosed by the presence of many glycosides; the potential mutagenicity of P. sepium was investigated both in vitro and in vivo. The results of that study, published in Environmental Health & Toxicology (2012), found a lack of mutagenicity potential — however, this does not address the established cardiotoxic risks at higher doses.

8.6 Drug-Drug Interaction: Digoxin

A critical pharmacological interaction concern involves concurrent use with cardiac glycoside drugs, particularly digoxin. Periploca sepium (Xiangjiapi) contains cardiac glycoside components that inhibit Na+/K+-ATPase; synergistic drug effects increase the risk of digoxin poisoning. Because periplocymarin and related compounds share the same mechanism of action as digoxin (Na+/K+-ATPase inhibition), co-administration could result in additive or synergistic cardiotoxic effects.

8.7 Adulteration and Misidentification: A Documented Safety Hazard

The most clinically documented safety issue involving Chinese silkvine in Western markets arises not from its intentional use, but from its use as an adulterant in products labeled as eleuthero (Siberian ginseng, Eleutherococcus senticosus). Adulteration of eleuthero root with Periploca sepium has been documented in the medicinal plant literature.

A particularly significant incident underscores the severity of this risk. There was a case of neonatal androgenization associated with maternal eleuthero use in Canada; subsequent analysis demonstrated that the implicated material was from Periploca sepium Bunge, a toxic plant containing cardiac glycosides and pregnane-type steroids. Neonatal androgenization was associated with the ingestion of a product during pregnancy labeled as containing Siberian ginseng; the image on the product was of an actual ginseng plant and analysis indicated that neither eleuthero nor ginseng compounds were present, but that Chinese silk vine (Periploca sepium) was present.

A case report indicated oral use of eleuthero concomitantly with digoxin might result in dangerously high blood levels of digoxin; however, it is likely the product used was adulterated with a botanical often confused with eleuthero, called Wu jia (Periploca sepium), a plant known to contain digitalis glycosides that could account for the adverse drug effects.

The American Herbal Products Association (AHPA) lists Periploca sepium root as a reported adulterant of eleuthero root bark in its Botanical Identity References Compendium, and recommends appropriate analytical steps to assure raw materials are free of this adulterant.

8.8 Variability of Periplocin Content

Only 4-methoxysalicylaldehyde is assigned as the index component for the quality evaluation of P. sepium root bark in the Chinese Pharmacopoeia (2015 Version), which requires its content to be not less than 0.20%; other components characterized by a high content, favorable pharmacological activity or potential toxicity should perhaps also be used as legal quality evaluation indicators. Researchers have noted that geographic differences in growing regions affect periplocin content, making it difficult to control toxic risks across commercial material from different provinces.

9. Research Gaps and Current Status

To date, some toxicity studies on cardiac glycosides from the genus Periploca have been carried out, but toxicity tests on other compounds are absent; comprehensive and in-depth investigations of the pharmacokinetics are needed to improve the safety of clinical therapy.

In view of the medical and agricultural value of the genus Periploca, in-depth investigations of the pharmacology in vivo, the mechanisms of biological actions, and the pharmacokinetics of the active ingredients should be carried out in the future; in order to ensure the safety of clinical medication, the potential toxicities of cardiac glycosides or other compounds should also be attended to; this systematic review provides an important reference base for applied research on pharmaceuticals and pesticides from this genus.

The most significant evidence gap is the complete absence of published human clinical trials for any indication — rheumatoid arthritis, cardiotonic use, anticancer, or immunomodulation — using standardized preparations of Cortex Periplocae or its isolated constituents. All mechanistic and efficacy evidence is preclinical, derived from cell cultures, animal models, or pharmacokinetic studies in rodents. Clinical translation remains at an early stage, and the narrow therapeutic margin imposed by the cardiotoxicity of periplocin presents a fundamental challenge for human use.

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