Herb Root (根 gēn)

Chang Shan

Dichroa root · 常山

Dichroa febrifuga Lour. · Radix Dichroae

Also known as: Heng Shan (恒山), Huang Chang Shan (黄常山), Ji Gu Chang Shan (鸡骨常山)

Chang Shan (Dichroa root) plant

Images shown are for educational purposes only

Chang Shan is a powerful and toxic herb that has been used for over two thousand years as China's premier anti-malarial remedy. Its alkaloids are among the most potent natural anti-malarial substances ever discovered. Because it can cause strong nausea and vomiting, it is used with caution, typically in processed form and only in robust patients, never in the weak or elderly.

Category Emetic herbs (涌吐药)
Therapeutic focus Malaria Support Respiratory phlegm conditions Fever Management

TCM Properties

Temperature

Cold

Taste

Bitter (苦 kǔ), Acrid / Pungent (辛 xīn)

Channels entered

Lungs, Liver, Heart

Parts used

Root (根 gēn)

Educational content • Consult qualified TCM practitioners for diagnosis and treatment

What This Herb Does

Every herb has a specific set of actions — here's what Chang Shan does in the body, explained in both everyday and TCM terms

Therapeutic focus

In practical terms, Chang Shan is primarily used to support these areas of health:

Malaria Support Respiratory phlegm conditions Fever Management

TCM Actions

In TCM terminology, these are the specific therapeutic actions that Chang Shan performs to restore balance in the body:

Checks Malaria Induces Vomiting to Expel Phlegm Clears Heat

How these actions work

'Intercepts malaria' (截疟 jié nüè) is the primary and most famous action of Chang Shan. 'Intercepting' means forcefully halting the cyclical pattern of alternating chills and fever characteristic of malaria. In TCM, malaria is understood as a pathogen lodged between the body's interior and exterior (the 'half-exterior, half-interior' level), often entangled with accumulated phlegm. Chang Shan disrupts this cycle by expelling the pathogenic factor and clearing the phlegm that fuels recurrent attacks. This action has been validated by modern pharmacological research showing that its alkaloids (particularly febrifugine/dichroine) have potent anti-malarial activity far exceeding that of quinine.

'Expels phlegm by inducing vomiting' (涌吐痰涎 yǒng tù tán xián) means that Chang Shan, especially in its raw (unprocessed) form, has a strong upward-driving quality that forcefully pushes accumulated phlegm and fluid out of the chest through vomiting. This was traditionally used for thick, stubborn phlegm lodged in the chest and diaphragm causing fullness, nausea, and inability to eat. This emetic action is powerful and can be harsh on the body, which is why the raw form is rarely used today and wine-processed or vinegar-processed forms are preferred. Pairing with Gan Cao (licorice root) actually intensifies the vomiting effect rather than moderating it.

'Clears Heat' reflects Chang Shan's cold nature. It can bring down fever, which is particularly relevant in the context of malarial fevers. Modern studies confirm it has significant antipyretic activity. However, because of its toxicity, it is not used as a general Heat-clearing herb and is reserved specifically for malaria and related conditions.

Patterns Addressed

In TCM, symptoms cluster into recognizable patterns of disharmony. Chang Shan is used to help correct these specific patterns.

Why Chang Shan addresses this pattern

In TCM, malaria is classically understood as a pathogen lodged in the Shao Yang (half-exterior, half-interior) level, entangled with accumulated phlegm-fluid. The cyclical alternation of chills and fever reflects the pathogen oscillating between the exterior and interior. Chang Shan's bitter, pungent, and cold nature enables it to penetrate this half-exterior, half-interior zone, forcefully expel the accumulated phlegm that harbors the pathogen, and clear the Heat driving the febrile episodes. Its pungent taste disperses and opens what is blocked, while its bitter taste descends and drains, and its cold nature directly counters the Heat component. This is why it is the premier 'malaria-intercepting' herb in the entire Materia Medica.

A practitioner would look for one or more of these signs

Chills

Cyclical attacks with regular timing

Nausea

Chest fullness with nausea before attacks

Excessive Phlegm

Thick phlegm accumulation in the chest

Intermittent Fever That Worsens Upon Exertion

Fever recurring every day, every other day, or every third day

Commonly Used For

These are conditions where Chang Shan is frequently used — but only when they arise from the specific patterns it addresses, not in all cases

Arises from: Phlegm

TCM Interpretation

TCM has recognized malaria (疟疾 nüè jí) for over two thousand years, describing it as a disease caused by a specific malarial pathogen (疟邪) that lodges in the space between the body's interior and exterior. The pathogen interacts with accumulated phlegm and fluid in the body, and the cyclical alternation of chills and fever reflects the struggle between the body's defensive Qi and the pathogen as it oscillates between interior and exterior. When the pathogen moves outward, it conflicts with defensive Qi at the surface, causing chills; when it turns inward, it generates Heat, causing fever. Phlegm accumulation in the chest and Spleen is considered a key factor that allows the disease to persist and recur.

Why Chang Shan Helps

Chang Shan directly addresses the core pathomechanism of malaria in TCM. Its cold nature counters the Heat generated during febrile episodes. Its pungent taste disperses and drives the pathogen out from its hiding place between interior and exterior. Its bitter taste drains and expels the accumulated phlegm that harbors the malarial pathogen and perpetuates the cycle. Modern research has confirmed that its alkaloids (febrifugine, isofebrifugine) have extremely potent anti-plasmodial activity, with some alkaloid fractions showing activity up to 100-150 times that of quinine in animal malaria models. Chang Shan is typically combined with herbs like Cao Guo (Tsaoko fruit), Bing Lang (betel nut husk), and Qing Hao (sweet wormwood) to enhance the anti-malarial effect while managing side effects.

Also commonly used for

Intermittent Fever That Worsens Upon Exertion

Cyclical fevers with alternating chills, particularly those resembling malarial patterns

Scrofula

Classical indication for neck lumps and nodules (瘰疬), recorded in the Ben Cao texts

Herb Properties

Every herb has an inherent temperature, taste, and affinity for specific channels — these properties determine how it interacts with the body

Temperature

Cold

Taste

Bitter (苦 kǔ), Acrid / Pungent (辛 xīn)

Channels Entered

Lungs Liver Heart

Parts Used

Root (根 gēn)

Dosage & Preparation

These are general dosage guidelines for Chang Shan — always follow your practitioner's recommendation, as dosages vary based on the formula and your individual condition

Standard dosage

5-9g

Maximum dosage

Do not exceed 9g in standard decoction. Zhang Xichun historically used up to 15-18g (五六钱) for severe malaria, divided into 5-6 small doses taken gradually, but this requires expert supervision and is not standard practice.

Dosage notes

Raw (unprocessed) Chang Shan has the strongest emetic and antimalarial action but also the highest toxicity. Wine-processed (酒常山) or vinegar-processed (醋常山) forms have reduced toxicity and emetic side effects, and are preferred for antimalarial use, though their efficacy is also reduced. For phlegm accumulation with chest oppression, smaller doses (around 3-5g) may be combined with Gan Cao and honey to induce controlled vomiting (an older technique now rarely used). For malaria (截疟), the standard approach uses the processed form at 5-9g, often in combination with Zhi Mu, Bei Mu, Cao Guo, and Bing Lang in the classic formula Chang Shan Yin. Zhang Xichun recommended dividing the total dose into multiple small servings taken gradually (徐徐温饮) to avoid emesis while maintaining efficacy.

Preparation

When used in decoction for malaria, Chang Shan is traditionally soaked in wine overnight before decocting, or the finished decoction has a spoonful of aged wine (陈酒) added near the end of cooking. This wine preparation helps moderate the emetic action. The decoction is classically taken cold or at room temperature, often the morning before meals, and traditionally left out overnight under the stars (露星月一宿) before drinking — a ritual associated with malaria formulas. When used raw for its emetic action (涌吐), it is simply decocted without special processing.

Processing Methods

In TCM, the same herb can be prepared in different ways to change its effects — here's how processing alters what Chang Shan does

Processing method

Chang Shan slices are mixed with rice wine (huangjiu), allowed to soak until the wine is absorbed, then stir-fried over low heat until dry. Standard ratio: 10kg rice wine per 100kg of herb slices.

How it changes properties

Wine processing moderates the herb's harshly ascending, emetic quality. The thermal nature remains cold but the action becomes somewhat milder. The upward-driving, vomit-inducing force is reduced, while the malaria-intercepting action is preserved. Toxicity is also reduced compared to the raw form. Alkaloid content decreases (approximately 1.4-1.9 times lower than raw), so larger doses may be needed.

When to use this form

The preferred form when the goal is malaria treatment (intercepting malaria) rather than inducing vomiting. This is the most commonly used processed form in clinical practice. Used in formulas like Jie Nue Qi Bao Yin.

Common Herb Pairs

These ingredients are traditionally combined with Chang Shan for enhanced therapeutic effect

Bing Lang
Bing Lang 1:1 (equal parts)

Chang Shan expels phlegm upward and intercepts the malarial cycle, while Bing Lang drives downward to break up food stagnation and phlegm accumulation in the Spleen. Together, they address phlegm from both above and below, preventing the phlegm from simply being driven in one direction. Bing Lang's descending nature also helps counteract Chang Shan's tendency to cause vomiting.

When to use: Malaria with significant phlegm accumulation, particularly in formulas like Jie Nue Qi Bao Yin. Used when there is chest fullness, nausea, and cyclical fevers.

Cao Guo
Cao Guo 1:1 (equal parts)

Chang Shan is cold and targets hot phlegm and heat-type malaria, while Cao Guo is warm, aromatic, and powerfully dries dampness and dispels cold. Together they cover both the heat and dampness aspects of malarial illness and can treat a wider range of malaria types, including damp-cold malaria and miasmic (瘴) malaria.

When to use: Malaria with both heat and dampness components, or malarial fevers in tropical/subtropical environments where dampness is a major factor. This pair forms the core of Jie Nue Qi Bao Yin.

Bie Jia
Bie Jia 1:1 (Chang Shan 30g : Bie Jia 30g)

Chang Shan clears Heat, expels phlegm, and intercepts malaria, while Bie Jia (soft-shelled turtle shell) nourishes Yin, subdues Yang, and softens hardness. Together, they address chronic malaria that has formed a 'malaria mother' (疟母), a palpable abdominal mass resulting from long-standing disease with Yin deficiency and blood stasis combined with phlegm accumulation.

When to use: Chronic, long-standing malaria that has not resolved, with palpable masses under the ribs (splenomegaly), Yin deficiency signs, and lingering low-grade fevers.

Gan Cao
Gan Cao 8:1 (Chang Shan 120g : Gan Cao 15g, as per the Bu Que Zhou Hou Fang)

Paradoxically, this pairing intensifies rather than moderates Chang Shan's emetic action. Together they forcefully induce vomiting to expel stubborn phlegm and fluid accumulated in the chest. This is a classical emetic (涌吐) combination rather than a harmonizing one.

When to use: When the therapeutic goal is specifically to induce vomiting to clear thick phlegm blocking the chest and diaphragm. This is an older application that is rarely used in modern practice.

Key Formulas

These well-known formulas feature Chang Shan in a prominent role

Jie Nue Qi Bao Yin 截疟七宝饮 King

This is the most famous formula featuring Chang Shan. Originally from Yang Shi Jia Cang Fang, it pairs Chang Shan with Cao Guo, Bing Lang, Hou Po, Qing Pi, Chen Pi, and Zhi Gan Cao to intercept malaria and expel phlegm-dampness. Chang Shan serves as King (alongside Cao Guo and Bing Lang), directly showcasing its core malaria-intercepting and phlegm-expelling actions. The formula is taken cold before the expected malarial attack.

Comparable Ingredients

These ingredients have overlapping uses — here's how to tell them apart

Cao Guo
Chang Shan vs Cao Guo

Both Chang Shan and Cao Guo intercept malaria and expel phlegm, but they target different malaria types. Chang Shan is cold, bitter, and pungent, making it suited for heat-type malaria (热疟) and damp-heat malaria where fever predominates and hot phlegm accumulates. Cao Guo is warm, pungent, and aromatic, making it suited for cold-damp malaria and miasmic malaria (瘴疟) where chills predominate and cold-damp phlegm obstructs. Chang Shan is also significantly more toxic and has a strong emetic effect, while Cao Guo is much gentler and also serves as a digestive spice.

Qing Hao
Chang Shan vs Qing Hao

Both are premier anti-malarial herbs with cold natures. Qing Hao (Artemisia annua) clears deficiency-type Heat and penetrates the Yin level to clear lurking Heat, making it better for cases with Yin deficiency, low-grade fevers, night sweats, and bone-steaming sensations. Chang Shan is more forceful, targeting substantial phlegm accumulation and acting as both an emetic and a malaria interceptor. Qing Hao is far gentler, non-toxic, and can be used long-term, while Chang Shan is toxic, harsh, and only for short-term use in robust patients.

Bing Lang
Chang Shan vs Bing Lang

Both are used in malarial formulas. Chang Shan directly intercepts malaria and drives phlegm upward, making it the primary anti-malarial agent. Bing Lang primarily kills parasites and drives stagnation downward. Chang Shan targets the phlegm-heat pathomechanism, while Bing Lang addresses the food stagnation and dampness that often accompany malarial illness. They are more commonly used together as a pair than as substitutes for each other.

Common Substitutes & Adulterants

Related species and common adulterations to be aware of when sourcing Chang Shan

Chang Shan (常山, Dichroa febrifuga) should not be confused with Hai Zhou Chang Shan (海州常山, Clerodendrum trichotomum), which belongs to an entirely different plant family (Lamiaceae/Verbenaceae). Hai Zhou Chang Shan is used to treat hypertension and has completely different chemistry and indications. The two share the name "Chang Shan" but are unrelated botanically and pharmacologically. Authentic Chang Shan can be identified by its characteristic chicken-bone-like twisted root morphology, hard woody texture with powdery fracture, and yellowish-white cross-section with distinct radial lines. Shu Qi (蜀漆), the leaf and young branch of the same plant, is a related but distinct medicinal product with stronger emetic properties.

Educational content — always consult a qualified healthcare provider or TCM practitioner before using any herb.

Toxicity Classification

Classical Chinese pharmacopoeia toxicity rating for Chang Shan

Toxic

The principal toxic constituents are the quinazolinone alkaloids: dichroine alpha (常山碱甲), dichroine beta/febrifugine (常山碱乙), and dichroine gamma/isofebrifugine (常山碱丙). These alkaloids stimulate vagal and sympathetic nerve endings in the gastrointestinal tract, reflexively inducing severe nausea and vomiting. Ingestion of as little as 10g of the dried root can cause toxicity. Toxicity symptoms include: nausea, vomiting, abdominal pain, diarrhea, bloody stool, gastrointestinal mucosal hemorrhage, palpitations, cardiac arrhythmia, hypotension, cyanosis, and in severe cases circulatory collapse and death. Chronic administration causes liver degeneration and kidney damage in animal models. The oral LD50 of dichroine beta in mice is approximately 6.57 mg/kg, roughly 150 times more toxic than quinine. Processing with wine (酒制) or vinegar (醋制) reduces the alkaloid content and toxicity by 5.5 to 7.5 times compared to the raw herb, though it also reduces antimalarial efficacy. Zhang Xichun advocated using small raw doses divided into multiple servings rather than relying on processing, as this preserved efficacy while limiting emesis.

Contraindications

Situations where Chang Shan should not be used or requires extra caution

Avoid

Pregnancy. Chang Shan alkaloids stimulate uterine contractions in both pregnant and non-pregnant animal models. The herb is classified as absolutely contraindicated during pregnancy.

Avoid

Severe Qi deficiency, chronic debility, or constitutional weakness. Classical texts warn against use in the elderly and those with longstanding illness, as the herb's drastic emetic action can further deplete the body's Qi and fluids.

Avoid

Liver or kidney impairment. The toxic alkaloids (particularly dichroine/febrifugine) are distributed primarily to the kidneys, heart, and liver, and repeated dosing causes hepatic and renal damage in animal studies.

Caution

Spleen and Stomach deficiency with poor digestion. Chang Shan's bitter-cold nature and strong emetic properties can severely aggravate nausea, vomiting, and gastrointestinal distress in patients with weak digestion.

Caution

Use with Gan Cao (licorice root). Classical sources note that combining Chang Shan with Gan Cao invariably induces vomiting.

Caution

Children. Due to its toxicity and strong emetic action, use in children requires extreme caution and significantly reduced dosage under strict practitioner supervision.

Caution

Excessive or prolonged use. Even in otherwise appropriate patients, large doses or extended courses increase the risk of gastrointestinal mucosal damage, bleeding, hypotension, and cardiac arrhythmia.

Classical Incompatibilities

Traditional Chinese pharmacological incompatibilities — herbs or substances to avoid combining with Chang Shan

Chang Shan does not appear on the classical Eighteen Incompatibilities (十八反) or Nineteen Mutual Fears (十九畏) lists. However, classical dietary prohibitions state that Chang Shan should not be taken with scallions (葱) or Chinese cabbage (菘菜). Additionally, combining it with Gan Cao (甘草, licorice) is noted to invariably cause vomiting, though this is a clinical caution rather than a formal incompatibility listing.

Special Populations

Important considerations for pregnancy, breastfeeding, and pediatric use

Pregnancy

Contraindicated. Pharmacological studies show that Chang Shan alkaloids (dichroine alpha, beta, and gamma) stimulate uterine contractions in pregnant rabbits and rats. The effect on pregnant uterus is comparable to equivalent doses of quinine. The herb's strong emetic action and gastrointestinal toxicity pose additional risks during pregnancy. All classical and modern Chinese materia medica sources list pregnancy as a contraindication (孕妇忌用).

Breastfeeding

No specific safety data exists for the use of Chang Shan during breastfeeding. Given the herb's known toxicity, the presence of alkaloids that are rapidly absorbed and distributed to multiple organs, and the lack of data on transfer into breast milk, it should be avoided during breastfeeding. The strong emetic and gastrointestinal effects in the mother also make it unsuitable during this period.

Children

Chang Shan is generally not recommended for children due to its toxicity and strong emetic action. If used under strict practitioner supervision for severe conditions, dosage must be substantially reduced according to the child's age and weight. Classical sources specifically warn against use in those with weak constitutions, which includes most young children.

Drug Interactions

If you are taking pharmaceutical medications, be aware of these potential interactions with Chang Shan

Antihypertensive medications: Chang Shan alkaloids lower blood pressure through vasodilation and cardiac suppression in animal studies. Concurrent use with antihypertensive drugs may cause excessive hypotension.

Cardiac glycosides and antiarrhythmic drugs: The herb's alkaloids can suppress cardiac function and cause arrhythmia. Combined use with drugs such as digoxin or antiarrhythmic agents may increase the risk of cardiac adverse effects.

Anticoagulant and antiplatelet medications: At toxic doses, Chang Shan can cause gastrointestinal mucosal hemorrhage. Patients on warfarin, heparin, or antiplatelet drugs face increased bleeding risk.

Hepatotoxic and nephrotoxic drugs: Given the herb's potential for liver and kidney damage, concurrent use with other hepatotoxic or nephrotoxic medications should be avoided.

Dietary Advice

Foods and dietary considerations when taking Chang Shan

Classical dietary prohibitions specify that scallions (葱) and Chinese cabbage (菘菜, Song Cai) should be avoided while taking Chang Shan. Hot tea should also be avoided on the day of taking the herb, particularly when used for malaria. Warm rice porridge (温粥) is recommended at midday after taking the medicine. In general, cold, raw, greasy, and hard-to-digest foods should be avoided to reduce gastrointestinal irritation, given the herb's inherent tendency to cause nausea and vomiting.

Botanical Description

Physical characteristics and morphology of the Chang Shan source plant

Dichroa febrifuga Lour. is a deciduous shrub in the Hydrangeaceae (formerly placed in Saxifragaceae) family, growing 0.4 to 2 meters tall. The stems are erect, round, and green, sometimes tinged purple, with short yellowish hairs when young and prominent nodes. The branches are cylindrical or slightly four-angled, becoming hairless with age. The leaves are opposite, elliptic to obovate, with serrate margins.

The plant bears small light-blue to purple flowers in terminal or axillary cymes, followed by blue-colored berries. The medicinal root is thick, cylindrical, often curved and twisted (described classically as resembling chicken bones), woody, with greyish-brown to yellowish-brown bark and a yellow cross-section. It grows naturally in shaded, moist mountain forests, along streams, and in ravines at elevations of 900 to 2,400 meters, and is also cultivated under forest canopy.

Sourcing & Harvesting

Where Chang Shan is sourced, when it's harvested or collected, and how to assess quality

Harvesting season

Autumn (秋季). The roots are dug up, cleared of fibrous rootlets, washed, and sun-dried.

Primary growing regions

The best quality (dao di yao cai) Chang Shan comes from Sichuan (四川) and Guizhou (贵州) provinces. It is also produced in Hunan, Hubei, Guangxi, Yunnan, Jiangxi, Fujian, Guangdong, Shaanxi, and Anhui provinces. The plant is distributed more broadly across southern China and parts of Southeast Asia (Vietnam, Myanmar, India, the Philippines), but the Sichuan and Guizhou sources are traditionally considered superior.

Quality indicators

Good quality Chang Shan root is cylindrical, often curved and twisted, with a form classically described as resembling chicken bones (hence the alias Ji Gu Chang Shan, 鸡骨常山). The outer bark should be brownish-yellow with fine vertical striations. The root should be hard and firm, not easily broken. When snapped, it produces a clean break with powdery dust. The cross-section should be yellowish-white with clearly visible whitish radial ray lines in a spoke-like pattern. It should be virtually odorless, with a slightly bitter taste. Roots that are firm, solid (not hollow), and show a pale yellow cross-section are considered superior quality. Material listed in the Chinese Pharmacopoeia should meet standards for morphological identification and tissue powder characteristics.

Classical Texts

Key passages from the classical Chinese medical texts that describe Chang Shan and its therapeutic uses

Shen Nong Ben Cao Jing (《神农本草经》)

Original: 常山，味苦，寒。主伤寒寒热，温疟，鬼毒，胸中痰结，吐逆。一名互草。生川谷。

Translation: Chang Shan is bitter in flavor and cold in nature. It governs Cold Damage with alternating cold and heat, warm malaria, malign toxins, phlegm accumulation in the chest, and vomiting. It has the alternate name Hu Cao. It grows in river valleys.

Ben Cao Gang Mu (《本草纲目》) — Li Shizhen

Original: 常山生用则上行必吐，酒蒸炒熟则气稍缓，少用亦不致吐也。

Translation: When Chang Shan is used raw, it ascends and invariably causes vomiting. When steamed in wine or dry-fried until cooked, its nature becomes somewhat milder, and if used in small amounts it will not cause vomiting.

Yi Xue Zhong Zhong Can Xi Lu (《医学衷中参西录》) — Zhang Xichun

Original: 常山，善消脾中之痰，为治疟疾要药。少服，则痰可徐消，若多服即可将脾中之痰吐出，为其多服即作呕吐，故诸家本草谓其有毒。

Translation: Chang Shan excels at dissolving phlegm in the Spleen and is an essential medicine for treating malaria. In small doses, it gradually dissolves phlegm. In larger doses, it can expel phlegm from the Spleen through vomiting. Because large doses cause vomiting, the various materia medica texts say it is toxic.

Ben Cao Zheng Yi (《本草正义》)

Original: 恒山、蜀漆，本是一物，气味皆辛苦而寒，泄热破结，降逆下气，开痰逐水，其用皆同。

Translation: Heng Shan [Chang Shan] and Shu Qi [its leaf] are originally from the same plant. Both are acrid, bitter, and cold in nature, draining Heat, breaking accumulations, directing counterflow downward, opening phlegm, and expelling water — their uses are the same.

Historical Context

The history and evolution of Chang Shan's use in Chinese medicine over the centuries

Chang Shan is one of the oldest recorded antimalarial herbs in Chinese medicine. It was first documented in the Shen Nong Ben Cao Jing (circa 1st–2nd century CE), where it was classified as a "lower grade" (下品) herb — indicating potent but potentially dangerous therapeutic action. Its species name febrifuga, coined by the Portuguese Jesuit naturalist João de Loureiro in his 1790 Flora Cochinchinensis, literally means "fever-dispelling," reflecting its principal use. According to one traditional account, the herb was named after a monk from Changshan who discovered its medicinal properties.

The leaf of the same plant, known as Shu Qi (蜀漆), has been used interchangeably with the root since ancient times, though classically considered somewhat stronger in emetic action. In the 1940s, Chinese pharmacologists Jang Chong-su and colleagues at the National Medical College of Shanghai isolated the active alkaloids (dichroines/febrifugine) and demonstrated their potent antimalarial effects, making this one of the earliest instances of modern pharmacological validation of a classical Chinese herb. This research paralleled the wartime search for antimalarial agents and drew international scientific attention. The synthetic derivative halofuginone, developed in the 1960s, has since found wide application in veterinary medicine and is under investigation for cancer, fibrosis, and autoimmune diseases.

Modern Research

4 published studies investigating the pharmacological effects or clinical outcomes of Chang Shan

1

Molecular mechanism study: Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase (2012)

Keller TL, Zocber D, Dubber E, et al. Nature Chemical Biology, 2012, 8(3): 311-317.

This landmark study revealed the molecular target of febrifugine and its derivative halofuginone for the first time. The researchers showed that these compounds bind to glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting its prolyl-tRNA synthetase activity. This inhibition activates the amino acid response (AAR) pathway, which underlies the broad bioactivities of this compound family, including anti-inflammatory and antimalarial effects. The inhibition could be reversed by adding exogenous proline.

PubMed
2

Review: Dichroa febrifuga Lour. — botany, traditional use, phytochemistry, pharmacological activities, toxicology, and progress in reducing toxicity (2024)

Journal of Ethnopharmacology, 2024, 328: 118057.

This comprehensive review summarized current knowledge on Chang Shan, identifying over 30 chemical compounds (alkaloids, terpenoids, flavonoids). It confirmed that the alkaloids are both the basis of efficacy and the source of toxicity, capable of causing multiple organ damage including liver, kidney, and heart. Methods to reduce toxicity include structural modification, traditional processing, and dosage form changes.

PubMed
3

Review: Prospects of halofuginone as an antiprotozoal drug scaffold (2022)

Wu J, Hollinger J, Bonanno E, Jiang F, Yao P. Cells, 2023, 13(1): 35.

This review examined halofuginone, the synthetic derivative of febrifugine from Chang Shan, as an antiprotozoal agent. Halofuginone has reduced toxic side effects compared to the parent compound and has progressed to commercial veterinary use and human clinical trials for tumors and fibrosis. The review covers its mechanism of action through inhibition of prolyl-tRNA synthetase and its efficacy against malaria, coccidiosis, cryptosporidiosis, toxoplasmosis, and leishmaniasis.

PubMed
4

Review: The chemistry and biology of febrifugine and halofuginone (2014)

McLaughlin NP, Evans P, Pines M. Bioorganic & Medicinal Chemistry, 2014, 22(7): 1993-2004.

This review traced the history of febrifugine from its isolation from Dichroa febrifuga through to structural elucidation and the synthesis of halofuginone. It summarized the antimalarial structure-activity relationships of various febrifugine analogues and detailed halofuginone's anti-fibrotic activity through inhibition of Smad3 phosphorylation downstream of the TGF-beta signaling pathway.

PubMed

Research on individual TCM herbs is growing but still limited by Western clinical trial standards. These studies provide emerging evidence and should be considered alongside practitioner expertise.