Sarcandra glabra

Sarcandra glabra (Thunb.) Nakai

1. Identity and Botanical Description

Scientific name: Sarcandra glabra (Thunb.) Nakai.
Family: Chloranthaceae.
Genus: Sarcandra Gardner.

Sarcandra glabra (Thunb.) Nakai is a perennial evergreen herb categorised within the Sarcandra Gardner genus under the Chloranthaceae family. The plant is an evergreen shrub that grows up to 2 m tall and has glossy green leaves with a distinctive aroma. Indigenous to tropical and subtropical regions of East Asia and India, this species is extensively distributed across China, particularly in the southern regions (Sichuan, Yunnan, and Jiangxi). S. glabra resources are widely distributed throughout China, Japan, Korea, and Southeast Asia.

Common names: S. glabra is commonly called Zhong Jie Feng in Chinese; because its ripe fruits resemble shiny red coral beads, it is also known as Cao Shan Hu. After soaking S. glabra in hot water for a period of time, it emits an attractive aroma and is considered delicious, and thus is also regarded as tea in some areas, also known as Jiu Jie Cha.

Parts used and common preparations: The whole plant is the medicinal part used. The whole S. glabra plant and its water extract have been listed in the Chinese Pharmacopoeia, while its single prescription preparations, such as Zhongjiefeng tablets and Xiekang capsules, are mainly used to treat inflammation and immune-related diseases such as acute respiratory infections, thrombocytopenia, pneumonia, cellulitis, appendicitis, shigellosis, psoriasis, and malignancies. In recent decades, Zhongjiefeng injections made from S. glabra extract have been used to treat cancers including gastric cancer, colon cancer, pancreatic cancer, and leukemia. The plant is occasionally planted for ornamental purposes and is otherwise used to prepare medicinal tea.

2. Traditional and Historical Use

S. glabra has been used as a folk medicine since the Qing Dynasty, commonly applied by numerous ethnic groups in clinical practice in China, such as Han, Miao, Dong, Yao, and Zhuang, and has been officially listed in the Chinese Pharmacopoeia since 1977.

In addition to its high ornamental value, S. glabra has a rich history of use in traditional Chinese medicine, evident through its empirical prescriptions for various ailments like pneumonia, dysentery, fractures, bruises, numbness, amenorrhea, rheumatism, and other diseases. Traditionally, S. glabra is widely used to treat traumatic fracture, joint swelling and pain, sore throat, abscess, and bleeding disorders. It has been used in traditional Chinese medicine also for the treatment of bruises, bone fractures, arthritis, nausea, internal pain, and cough.

It has been proven in traditional practice to be effective in the treatment of cancer, pneumonia, appendicitis, gastritis, enteritis, diarrhea, rheumatism, and injuries from falls and fracture.

In modern clinical practice, it has also been applied to treat upper respiratory tract infection, pneumonia, gastritis, viral myocarditis, tumor, and thrombocytopenia, with significant clinical therapeutic effect.

The herb occupies a specific position within TCM theory: Sarcandra glabra, as a type of "antipyretic-detoxicate drug," has always been widely used in traditional Chinese medicine.

3. Key Constituents and Active Compounds

To date, over 400 compounds including terpenoids, coumarins, lignans, flavonoids, sterols, anthraquinones, organic acids, and organic esters have been isolated and characterised from S. glabra, some featuring unprecedented structures.

3.1 Sesquiterpenoids

Sesquiterpenoids are the most chemically distinctive and extensively studied class of compounds in S. glabra. A particular focus in the literature is on the unique chemotaxonomic marker of the plant: the lindenane-type sesquiterpenoids. The structures of these sesquiterpenoids can be divided into eight main skeletal types, namely eudesmane, lindenane, germacrane, eremophilane, aromadendrane, elemane, guaiane, and cadinene.

Two new sesquiterpenes, sarcandralactones A and B, and five new dimeric sesquiterpenoids, sarcandrolides A–E, along with 10 known compounds have been isolated from the whole plants of Sarcandra glabra. Some of the new isolates exhibit significant cytotoxicities when tested against a small panel of tumor cell lines.

Six new sesquiterpene glycosides — with eudesmanolide, elemanolide, lindenane, and germacranolide sesquiterpene aglycons — have been isolated from the whole plant of Sarcandra glabra.

More recently, three novel dimeric sesquiterpenoids named sarglanoids A–C, two undescribed monomeric sesquiterpenoids named sarglanoids D and E, and seven known compounds were isolated and characterized from Sarcandra glabra. Sarglaroid A was identified as a rare 8,9-seco lindenane dimer with a unique 5/5/5 tricyclic system.

3.2 Coumarins

Isofraxidin and fumaric acid are identified as two major active constituents of Sarcandra glabra. Isofraxidin has reported anticancer and cholagogic effects; fumaric acid has antibiosis, antalgic, and antitumor effects. Because of its strong pharmacological activity, isofraxidin is used as an index compound for controlling the quality of S. glabra and its preparations in the Chinese Pharmacopoeia. Studies have shown that isofraxidin has a wide range of pharmacological effects, including anti-inflammatory, antiviral, and anti-tumor effects, as well as inhibition of platelet aggregation. Furthermore, 3,3′-biisofraxidin has been reported to induce gastric cancer cell apoptosis by activating the mitochondrial-mediated apoptosis pathway.

From antibacterial-activity-guided fractionation, the coumarin compounds isolated include 4,4′-biisofraxidin (a novel natural product), esculetin, fraxetin, scoparone, isofraxidin, and scopoletin.

3.3 Phenolic Acids, Caffeoylquinic Acids, and Flavonoids

Caffeoylquinic acids, coumarins, and dicaffeoyl derivatives are considered to be three of the most abundant bioactive components in Sarcandra glabra. Rosmarinic acid and chlorogenic acid are among the most studied phenolic constituents. The S. glabra extract contains high levels of rosmarinic acid, isofraxidin, fumaric acid, terpenoid saponins, and others.

Additional phenolic compounds identified include: isoscopletin, syringaresinol monoside, styraxjaponoside B, 5-O-caffeoylshikimic acid, shizukanolide E, isoastilbin, neoisoastilbin, astilbin, and neoastilbin.

Methyl isorinate, a previously uncharacterised compound in S. glabra, suppresses NF-κB activation and reduces the expression of iNOS and COX-2 as well as the phosphorylation of IκB in LPS-treated RAW264.7 cells. In addition, the production of two inflammatory cytokines (IL-6 and TNF-α), as well as release of reactive oxygen species, in LPS-stimulated macrophages was also inhibited by this compound.

3.4 Polysaccharides

Polysaccharides isolated from S. glabra have attracted interest for immunomodulatory and anti-tumor activities. An acidic polysaccharide from S. glabra has exhibited anticancer effects in human osteosarcoma cells in vitro.

4. Mechanisms of Action

4.1 Anti-inflammatory Pathways

The combined anti-inflammatory effect of three typical constituents of S. glabra — chlorogenic acid, rosmarinic acid, and isofraxidin (C+R+I) — has been investigated. Targeting the MAPK-NF-κB pathway appears to be one major mechanism involved, as demonstrated using LPS-stimulated RAW264.7 cells as an in vitro model and LPS-induced acute lung injury in mice as an in vivo model. C+R+I significantly suppressed the levels of nitric oxide, pro-inflammatory cytokines, and inhibited iNOS and COX-2 expression. Western blot analysis showed that C+R+I suppressed phosphorylation of NF-κB and MAPK, including phosphorylation of p65-NF-κB, IKB, ERK, JNK, and P38.

Structure-activity relationships among isolated phenolic compounds from S. glabra have been analysed, and the results suggest that diverse phenolic compounds are collectively associated with the anti-inflammatory effects of S. glabra.

More recently, lindenane sesquiterpenoid dimers from the roots of S. glabra were shown to potently inhibit NO production, and one compound significantly inhibited the LPS-/ATP-induced IL-1β release by inactivating the NLRP3 inflammasome through inhibiting its initiation and assembly by affecting K⁺ efflux.

The anti-inflammatory activity of S. glabra proceeds via TLR4/NF-κB and MAPK pathways, while gastroprotective effects occur through mucosal repair, upregulation of tight junction proteins claudin-1 and occludin, and antioxidant activity; immunomodulatory effects involve Th17/Treg balance and secretory immunoglobulin A (SIgA) secretion.

4.2 Antitumour Pathways

S. glabra mainly plays an anti-tumour role by inhibiting proliferation, inducing apoptosis, inhibiting telomerase activity, and improving immune function. However, the active components, related targets, and signalling pathways of its antitumour effects are still not fully clear. Active components of the antitumour effect are suggested to include polysaccharides, flavonoids, rosmarinic acid, isofraxidin, 3,3′-biisofraxidin, and atractylenolide III, with mechanisms possibly related to regulating the ERK-eIF4F signalling pathway and apoptosis-related proteins including Bcl-2, Bax, and caspase-3.

Zhongjiefeng injection was reported to have a strong cytotoxicity on human lung cancer A-549, colon cancer HCT-29, and gastric cancer BGC-823, with IC₅₀ values less than 50 μg/mL. Zhongjiefeng tablets could induce p21 expression by up-regulating the TGF-β pathway and arrested A549 and H1299 cells in the G0/G1 phase, thus inducing cell apoptosis and inhibiting cell proliferation.

4.3 Antiviral Mechanisms

Isofraxidin treatment ameliorates LPS-induced inflammatory and oxidative stress damage in mice, reduces inflammatory markers (IL-6, TNF-α, IL-1β, IL-8, malondialdehyde, and IFN-γ), and prevents liver and lung tissue damage induced by LPS. Isofraxidin thus exhibits preventive and therapeutic properties against lipopolysaccharide-induced cytokine storms in mice via anti-inflammatory and antioxidant pathways.

In an animal study using a restraint-stress mouse model of influenza, S. glabra extract was administered orally for 10 consecutive days. Body weight, morbidity, and mortality were recorded, and histopathological changes, susceptibility gene expression, and inflammatory markers in lungs were assessed. Restraint stress significantly increased susceptibility and severity of influenza virus.

5. Scientific Evidence by Area of Use

5.1 Anti-inflammatory and Respiratory Infections

Preclinical evidence (in vitro / animal): Multiple in vitro studies have established anti-inflammatory mechanisms of key S. glabra constituents acting via NF-κB and MAPK signalling (see Section 4 above). Animal studies using rodent models of acute lung injury further support these observations. The herb also exhibits protective effects against viral pneumonia in preclinical settings.

Clinical evidence: S. glabra has been applied clinically to treat upper respiratory tract infection and pneumonia with significant claimed therapeutic effects, but these reports originate primarily from Chinese-language clinical observations rather than controlled trials. Most clinical evidence is derived from small-scale, non-randomised, or uncontrolled studies. Evidence strength: Preclinical evidence is moderately robust; adequately controlled human clinical trials are lacking.

5.2 Anti-tumour and Cancer Adjuvant Use

In vitro evidence: S. glabra inhibited tumour growth in human leukemic cell lines in vitro. An acidic polysaccharide from S. glabra exhibited anticancer effects in human osteosarcoma cells in vitro. S. glabra has been reported to inhibit the growth of gastric cancer, leukaemia, liver cancer, lung cancer and other malignant tumours, playing an anti-tumour role by regulating cell cycle and inducing cell apoptosis. Lindenane dimers from S. glabra inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC₅₀ values ranging from 5.4 to 10.2 μM.

In vivo and network pharmacology evidence: Network pharmacological analysis was used to identify the active components of S. glabra and their corresponding targets for the treatment of pancreatic cancer, and molecular docking, molecular dynamic simulations, and in vitro experiments were performed to validate the findings.

Human clinical evidence: Sarcandra glabra has not been shown to treat cancer in humans. It may reduce side effects from radiation treatment, but further studies are needed to confirm these effects. One human study found it reduced radiation therapy-induced mucositis and xerostomia in patients with advanced nasopharyngeal carcinoma. A clinical study investigated the protective effect of Compound Sarcandra Glabra on radiation injury of parotid glands in patients with nasopharyngeal carcinoma. Sixty patients with primary nasopharyngeal carcinoma were divided into a treatment group and a control group using a random number table, with all patients treated by a combination of 9-field intensity-modulated radiotherapy and chemotherapy.

Clinically, S. glabra and its various formulations (injections, tablets, granules, oral liquids) have been used as adjuvant therapy for nasopharyngeal, gastric, and colorectal cancers, showing improvements in clinical symptoms and quality of life. More studies are needed to confirm whether S. glabra can indeed control some cancer treatment-related symptoms and to further validate any antitumour potential. Evidence strength: Predominantly preclinical (in vitro and animal). The single human observation for radiation-induced mucositis is preliminary and requires replication in well-controlled trials. No clinical evidence establishes direct anti-cancer efficacy in humans.

5.3 Thrombocytopenia

S. glabra increases platelet production and may play a role in reducing chemotherapy-induced thrombocytopenia. Although S. glabra has been used in traditional Chinese medicine for this purpose, fully controlled clinical studies are limited.

A study investigated the effect of Sarcandra glabra on prevention and treatment of thrombocytopenia after chemotherapy with a large dosage. A BALB/c mouse model of thrombocytopenia was induced by intraperitoneal injection of 5-fluorouracil. S. glabra dilution was administered orally once daily from the beginning of the experiment, and peripheral blood cell counts were measured on days 2, 4, and 7. Bone marrow biopsy was employed on day 7 to investigate haematopoietic condition. Before the chemotherapy, platelet counts in the S. glabra-treated group were higher than in the control group (P < 0.05); after 5-FU chemotherapy, platelet counts were not significantly decreased. The study concluded that Sarcandra glabra Thunb had obvious activity in the treatment of thrombocytopenia and could prevent thrombocytopenia caused by 5-FU. This was an animal study; controlled human RCT evidence for this indication remains limited. Evidence strength: Preclinical (animal). Early clinical observations in Chinese medical literature exist, but large randomised controlled trials have not been published in indexed literature.

5.4 Gastrointestinal Conditions

Clinically, S. glabra and its various formulations have been used for infectious diarrhea, gastritis, and peptic ulcers. Its gastroprotective effects occur through mucosal repair, upregulation of tight junction proteins claudin-1 and occludin, and antioxidant activity.

Most clinical evidence for gastrointestinal conditions is derived from small-scale, non-randomised, or uncontrolled studies. Evidence strength: Preliminary; preclinical mechanistic data are available, but high-quality human trials are absent.

5.5 Hepatoprotection

Some constituents of S. glabra are reported to have hepatoprotective properties. Certain sesquiterpene lactones of Sarcandra glabra showed hepatoprotective activity against d-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial cells in vitro. Evidence strength: In vitro only; no human data.

5.6 Bone and Joint Conditions

Although S. glabra has been used in traditional Chinese medicine for the treatment of bone fractures and arthritis, clinical studies have not been conducted in humans. Evidence strength: Traditional use only; no human clinical data available.

5.7 Anti-diabetic Activity

In animal studies, S. glabra constituents demonstrate anti-diabetic activities. Modern pharmacological studies have shown that S. glabra has hypoglycemic and hypolipidemic properties. Evidence strength: Preclinical animal studies only; no controlled human evidence.

5.8 Oxidative Stress and Cytoprotection

In vitro studies suggest S. glabra can protect against oxidative stress in mesenchymal stem cells. Evidence strength: In vitro only.

6. Body Systems and Health Areas Associated with S. glabra

• Immune system: Immunomodulatory properties have been demonstrated in pharmacological studies.
• Haematological system: The anti-thrombocytopenic effect is among those confirmed in clinical practice.
• Respiratory system: Use in pneumonia, upper respiratory tract infections, and influenza-related conditions is supported by preclinical studies and clinical observations.
• Gastrointestinal system: Formulations have been used for infectious diarrhea, gastritis, and peptic ulcers.
• Oncology (adjuvant): Used as an adjunct in tumour management, particularly in TCM clinical practice in China.
• Musculoskeletal system: Traditional use for fractures, joint pain, and rheumatism.
• Hepatic system: Hepatoprotective effects identified in vitro.
• Metabolic system: Hypoglycaemic and hypolipidaemic effects in animal models.

7. Dosage Forms and Reported Dosages

The whole plant and preparations made from the whole plant of S. glabra, such as Zhongjiefeng extract, Zhongjiefeng tablets, and Xuekang capsules, are mainly used for the treatment of pharyngolaryngitis, acute influenza, pneumonia, shigellosis, cellulitis, appendicitis, thrombocytopenia, leukoderma vitiligo, and abscess, as recognised in the National Commission of Chinese Pharmacopoeia 2010.

Documented formulations include:

• Oral decoction / herbal tea: Prepared by soaking or decocting the dried whole plant in hot water.
• Tablets (Zhongjiefeng tablets / Zhongjiefeng Pian): Solid dosage forms manufactured from the dried aqueous extract.
• Capsules (Xiekang / Xuekang capsules): Encapsulated extract forms.
• Injection (Zhongjiefeng injection): Zhongjiefeng injection is a sterile aqueous solution processed through extraction of Herba Sarcandrae and is used for treating pneumonia, appendicitis, cellulitis, and bacillary dysentery, and can also be combined with Zhongjiefeng tablets in tumour treatment including digestive tract cancer, pancreatic cancer, and hepatocarcinoma.
• Granules and oral liquids: Various formulations including granules and oral liquids have been used clinically.

Regarding quality marker concentration: Isofraxidin is used as the official index marker for controlling the quality of S. glabra and its preparations in the Chinese Pharmacopoeia. In the preclinical thrombocytopenia study described above, the extract dilution was poured into the stomach of mice once daily from the beginning of the experiment. The specific mass dosage in that animal model was not converted to a human equivalent in the indexed literature reviewed.

In the combination anti-inflammatory study, the combined anti-inflammatory effect of three typical constituents — chlorogenic acid, rosmarinic acid, and isofraxidin (C+R+I) — from S. glabra was investigated in cell and animal models, but specific dosages in standardised human-applicable units are not established in the cited literature.

No officially recognised human therapeutic dosage range has been established by international regulatory bodies such as the WHO, EMA, or NIH for S. glabra as a dietary supplement outside of China. Dosages reported in the literature are derived from Chinese clinical practice records and animal experiments and should not be extrapolated to self-directed human supplementation without guidance from a qualified practitioner.

8. Safety Considerations

8.1 Acute and Subchronic Toxicology

From its long-term medicinal and edible history, S. glabra is considered to be a "medicine-food homology" herb with good safety. The maximum tolerance dose of aqueous extract of S. glabra in mice was established to be more than 20 g kg⁻¹ body weight, without obvious genetic toxic effect, and there was no pathological damage in rats fed with the extract for 90 days at dosages of 1.67, 3.33, and 5 g kg⁻¹ body weight. In those studies, the results of the acute toxicity test, genetic toxicity test, and teratogenicity test of aqueous extract of S. glabra were all negative, suggesting that S. glabra has almost no obvious toxicity.

8.2 Limitations of Existing Toxicological Data

These studies have only evaluated the toxicology of aqueous extract of S. glabra and have not yet systematically evaluated the toxicology of its ethanol extract or other extracts. Short-term use is generally well tolerated, with mild gastrointestinal discomfort being the most common adverse event reported; toxicological studies indicate low acute toxicity and no mutagenicity, but long-term safety and chronic toxicity data are lacking. Long-term adverse effects are unclear.

8.3 Drug Interactions and Special Populations

No formally characterised pharmacokinetic drug–drug interactions between S. glabra and conventional medicines have been documented in the peer-reviewed literature reviewed here. Given that isofraxidin inhibits platelet aggregation, there is a theoretical concern regarding additive effects with anticoagulant or antiplatelet medications, though this has not been directly studied in humans. Future research should prioritise systematic pharmacovigilance.

8.4 Regulatory Status

The herb has been officially listed in the Chinese Pharmacopoeia since 1977. The whole plant and its water extract have been listed in the Chinese Pharmacopoeia, and several single-prescription preparations are approved within China's national drug regulatory system. S. glabra does not appear in current WHO monographs, European Pharmacopoeia, or major Western regulatory pharmacopeias as of the time of the sources reviewed.

9. Evidence Limitations and Research Gaps

Findings on pharmacology and phytochemistry are still difficult to comprehensively reflect its pharmacological effects and mechanisms; most pharmacological studies are still focused on exploring the activity of crude extracts, and the correlation between pharmacological effects and chemical components has yet to be fully established. There are many issues that deserve further investigation.

The anti-tumour research on S. glabra is not comprehensive enough; its effective anti-tumour components and related mechanisms still need to be further studied. Future research should prioritise high-quality randomised controlled trials, systematic pharmacovigilance, and mechanistic studies focusing on gastrointestinal mucosal immunity and gut microbiota modulation.

References

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