How Has Sansuyu Stayed a Medicine for 2,000 Years? Old Herbal Records and Two Pharmacopoeia Markers

Ripe red sansuyu fruits on an autumn hillside appear in two very different kinds of records. One is a line of old Chinese materia medica (bencao) books going back nearly two thousand years. The other is the laboratory standard of today’s pharmacopoeias. What did the old books say the fruit was for? Did that description stay the same from age to age? And how do we judge the quality of sansuyu as a medicinal herb today? This article follows the path by which sansuyu came to be recorded as an herbal medicine along two lines: old texts and the molecules inside the fruit. Why its flowers open before its leaves in early spring is covered in Why Does Cornus officinalis Flower Before Its Leaves?, and why the seed is removed when the fruit becomes medicine is covered in Why Is the Seed Removed When Cornus officinalis Fruit Becomes Medicine?

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The First Record: A Sour Fruit in the “Middle Grade” of the Shennong Bencao Jing

Sansuyu is Cornus officinalis Siebold & Zucc., a member of the dogwood family (POWO). Its record as a medicine begins with the Shennong Bencao Jing (神農本草經), counted as the oldest surviving materia medica. The book appears to have gathered knowledge passed down around the first and second centuries AD, and it sorted 365 medicines into three grades: upper, middle and lower (Wikipedia). A modern research review also notes that the fruit was first recorded in this book and has been used for more than two thousand years since (Dong et al. 2018).

The original text no longer survives, but Li Shizhen’s Ming-dynasty Bencao Gangmu (本草綱目, Compendium of Materia Medica) copied the Shennong lines (abbreviated “Benjing”) at the head of its sansuyu entry. Under the heading it notes “Benjing, middle grade (中品).”

心下邪氣、寒熱，溫中，逐寒濕痺，去三蟲。久服輕身。(《本經》)

In plain words: “It treats harmful qi lodged below the heart, with chills and fever; it warms the middle; it drives out numbness and pain caused by cold and damp; and it expels the three worms (三蟲). Taken for a long time, it lightens the body.” Its taste was given as sour (酸) and its nature as balanced (平) (Bencao Gangmu, wood section). Another name the Shennong text gave it was shu suanzao (蜀酸棗), “the sour jujube of Shu,” and Li Shizhen explained that such names imitate the shape of the fruit.

One point deserves attention here. Words that people now associate with sansuyu, such as “essence” (精, jing) or “kidney” (腎, shen), do not appear in this first record.

Fifteen Hundred Years of Notes in One Entry

The Bencao Gangmu was completed in 1578 and first carved for printing in 1590 at Jinling, present-day Nanjing (Wellcome Collection description). Its sansuyu entry is not the account of a single author. In the “indications” (主治) section, it strings together sentences from physicians of earlier ages, in historical order and with their sources. Reading just this one section shows how the description of sansuyu built up over time.

Source	Period	What it added about sansuyu (gist)
Shennong Bencao Jing	Around the 1st–2nd century	Harmful qi below the heart, chills and fever; warms the middle; numbness from cold and damp; the three worms
Mingyi Bielu	Northern and Southern dynasties, compiled by Tao Hongjing	Strengthens yin (陰) and boosts essence (精); calms the five organs; stops overly frequent urination
Zhen Quan (甄權)	Sui–Tang	Adds to essence and marrow (精髓); stops urinary incontinence in the elderly
Daming (大明)	After the Tang	Warms the lower back and knees
Wang Haogu (王好古)	Yuan	Enters the foot-jueyin and foot-shaoyin channels, that is, the liver and kidney channels; its sour, astringent taste holds back what leaks away

The Mingyi Bielu is a book compiled by Tao Hongjing in the Northern and Southern dynasties period (ctext note on the Tangye Bencao), and Zhen Quan was a physician active in the Sui and early Tang. Read from top to bottom, the table shows a direction. At first sansuyu was a medicine that warmed the middle and eased numbness and pain; over time, descriptions of a medicine that boosts essence and holds back urine were added.

The line from the Yuan-dynasty physician Wang Haogu stands out. Author of the Tangye Bencao (湯液本草), he was a physician who organized which channel each medicine enters (ctext note). He wrote that sansuyu enters the liver (foot-jueyin) and kidney (foot-shaoyin) channels and explained that its sour, astringent taste “gathers in what slips away” (收滑) (Bencao Gangmu, wood section). The way today’s Chinese Pharmacopoeia summarizes sansuyu, as entering the liver and kidney channels to “tonify the liver and kidney, astringe and consolidate” (補益肝腎，收澀固脫) (Chinese Pharmacopoeia 2020), is closer to these later layers than to the first record.

Sansuyu also found a place inside formulas. The Kidney Qi Pill (腎氣丸) in the Jingui Yaolüe by the Han-dynasty physician Zhang Zhongjing consists of eight ingredients: rehmannia, Chinese yam, sansuyu, alisma, poria, tree peony root bark, cinnamon twig and aconite (National Research Institute of Chinese Medicine, Taiwan), and Wang Haogu also pointed out that sansuyu was used in this formula. The Song-dynasty physician Qian Yi’s “Rehmannia Pill” (地黃丸) is made of six ingredients, the Kidney Qi Pill without cinnamon twig and aconite, and this formula, published in 1119 in the Xiao’er Yao Zheng Zhi Jue (小兒藥證直訣), is what is now called Liuwei Dihuang Wan (Wikipedia). The original amounts are eight qian of prepared rehmannia, four qian each of sansuyu and Chinese yam, and three qian each of alisma, tree peony root bark and poria (Xiao’er Yao Zheng Zhi Jue), so sansuyu makes up 16% of the total of twenty-five qian.

What Did the Dongui Bogam Choose to Record?

Heo Jun of Joseon Korea completed the Dongui Bogam (東醫寶鑑) in 1610; it was printed in 1613 and inscribed on UNESCO’s Memory of the World Register in 2009 (UNESCO). Sansuyu has an entry in the tree section of its volumes on medicinal substances (湯液篇, Tangaek-pyeon).

山茱萸 性微溫 味酸澁 無毒 强陰益精 補腎氣 … 添精髓 煖腰膝 助水藏 止小便利 老人尿不節 除頭風鼻塞耳聾

This means: “Its nature is slightly warm, its taste sour and astringent, and it is not toxic. It strengthens yin, boosts essence and supplements kidney qi. … It adds to essence and marrow, warms the lower back and knees, stops overly frequent urination and urinary incontinence in the elderly, and relieves head wind, nasal congestion and deafness” (Dongui Bogam, Tangaek-pyeon; part omitted). At the end the entry names its sources as “Bencao” (本草) and “Rumen” (入門), that is, earlier materia medica and the Ming-dynasty medical text Yixue Rumen, and it also records another name, seokjo (石棗), “stone jujube.”

Set beside the table above, the entry shows what the Dongui Bogam chose. It carried over almost word for word the notes on essence and kidney, lower back and knees, and urine added by the Bielu, Zhen Quan and Daming, but it left out the first line of the Shennong Bencao Jing, “warms the middle and treats numbness and worms.” Heo Jun’s understanding of sansuyu was closer to the descriptions built up later than to the first record of two thousand years earlier.

All of these descriptions, however, summarize the theory and experience of traditional medicine. The effects written in the old books are not the same as treatment effects proven in modern clinical trials, and the two need to be read separately.

Two Molecules in the Fruit: Loganin and Morroniside

Now let us move from texts to molecules. About 90 compounds have so far been isolated and identified from sansuyu fruit. They include terpenoids, flavonoids, tannins, polysaccharides and organic acids, but only about 18% of them have actually been tested for biological activity (Dong et al. 2018). Of these, the components the pharmacopoeias chose as standards are two iridoid glycosides: loganin and morroniside.

Both molecules consist of an iridoid part with a glucose attached. The Korean Pharmacopoeia gives their formulas as loganin, C₁₇H₂₆O₁₀ (molecular weight 390.38), and morroniside, C₁₇H₂₆O₁₁ (406.38) (Korean Pharmacopoeia). The difference of 16.00 between the two weights equals the weight of one oxygen atom. But one oxygen apart does not mean alike in shape. Loganin has a ring of five carbon atoms, whereas morroniside has a six-membered ring containing oxygen in that place and is classed among the secoiridoids (Czerwińska & Melzig 2018).

Loganin is not unique to sansuyu. Its very name comes from the Loganiaceae family, and it was first isolated from the seeds of the strychnine tree (Strychnos nux-vomica). In many plants it also serves as an intermediate step in making other substances (Wikipedia, “Loganin”). Loganin alone, therefore, can hardly single out sansuyu.

How Does It Differ from Its European Cousin, the Cornelian Cherry?

A close relative of sansuyu, the cornelian cherry (Cornus mas), grows in Europe and Southwest Asia. It belongs to the same genus, its red fruit looks similar, and it too has long been used medicinally in Europe. According to a review comparing the fruit chemistry of the two species, iridoids such as loganin, loganic acid, cornin, sweroside and cornuside are found in both. The most abundant iridoid in cornelian cherry fruit was loganic acid. By contrast, less widely known iridoids such as morroniside, as well as tannins, were detected particularly in sansuyu fruit (Czerwińska & Melzig 2018). Another review from 2021 also presents morroniside and several other iridoid glycosides as characteristic of sansuyu (Gao et al. 2021).

This, however, summarizes the analyses reported so far; it is not proof that cornelian cherry contains no morroniside at all. Still, the fact that morroniside marks sansuyu better than loganin does offers a clue as to why the pharmacopoeias pair these two components.

How Do Pharmacopoeias Measure Sansuyu?

The Korean Pharmacopoeia checks sansuyu in two steps (Korean Pharmacopoeia). The first is an identification test. A solution made by steeping the powdered herb in ethanol and solutions of loganin and morroniside reference standards are spotted side by side on a thin silica gel plate and developed with a solvent. Under ultraviolet light (254 nm), two of the herb’s spots must appear with the same color and at the same height as the spots of the two standards. This method is called thin-layer chromatography.

The second step is an assay that measures the amount. A methanol extract of the powdered herb is run through the narrow column of a high-performance liquid chromatography (HPLC) instrument to separate its components, and their amounts are measured by how much light they absorb at a wavelength of 240 nm. Under these conditions morroniside leaves the column first and loganin after it, leaving two peaks on the record. The amounts calculated by comparing the areas of the two peaks with the standards must add up to at least 1.2%. That means 100 g of the dried herb must contain at least 1.2 g of the two components combined.

The 2020 edition of the Chinese Pharmacopoeia also sets the sum of the same two components at no less than 1.2%. In the Chinese Pharmacopoeia, morroniside is called 莫诺苷 and loganin 马钱苷. Interestingly, it sets a separate, lower standard of 0.70% for “wine-processed” sansuyu (酒萸肉), which is stewed or steamed with wine (Chinese Pharmacopoeia 2020). The pharmacopoeia does not give the reason, but it is clear that it treats the component standard differently depending on how the same fruit is processed.

The term “marker component” is easy to misread. It does not mean the two components explain all of sansuyu’s effects. It means they are markers for confirming that the herb really is sansuyu and that it meets the required quality.

How Far Has Research Come?

Loganin and morroniside are actively studied in the laboratory. Many cell and animal experiments related to blood sugar, the kidneys and inflammation have been reported (Gao et al. 2021; Dong et al. 2018). But most of these results are at the cell or animal stage, and only some of the compounds found in the fruit have been tested for activity at all. Such results should not be read directly as effects that appear in people.

Summary: Two Thousand Years of Sentences and a 1.2% Threshold

The path by which sansuyu has remained a medicinal herb can be summed up in two kinds of records. One is a layering of sentences. The first record, in the Shennong Bencao Jing, described a medicine that warmed the middle and eased numbness and pain; the Mingyi Bielu and physicians of the Tang and Yuan added, in turn, notes on essence and kidney, urine and channels. The Dongui Bogam selected the later layers among them. The other is a molecular threshold. Today’s pharmacopoeias confirm the herb sansuyu with two spots in an identification test, two peaks in liquid chromatography, and their sum of 1.2%.

Over two thousand years, people recorded in sentences what they observed about one small red fruit that God made, and today they have written into pharmacopoeias how to measure the molecules inside it. Telling apart what is old theory, what is measured fact and what is still under study is also part of learning about this fruit properly.

Correction · 2026-10-05 We corrected the statement that the Dongui Bogam described sansuyu as an herb “acting on the liver and kidney” to match the original text; the note about the liver and kidney channels is found in the record of the Yuan-dynasty physician Wang Haogu. We removed an unverified statement that sansuyu appears in the Hyangyak Jipseongbang. Material on flowering, seed removal and Gurye that overlapped with other articles was shortened and linked to those articles. In its place we added the original texts of the Bencao Gangmu and Dongui Bogam, the pharmacopoeia identification test and content standard (at least 1.2% of the two components combined), and a chemical comparison with the cornelian cherry, and we replaced the photographs.

References

• Bencao Gangmu (本草綱目), Wood Section 3, Shanzhuyu — Wikisource
• Dongui Bogam, Tangaek-pyeon Vol. 3, Sansuyu — Wikisource (in Korean)
• Donguibogam: Principles and Practice of Eastern Medicine — UNESCO Memory of the World
• Wikipedia: Shennong Bencaojing
• Tangye Bencao (湯液本草), introductory note — Chinese Text Project
• Modern research on the Jingui Kidney Qi Pill — National Research Institute of Chinese Medicine, Taiwan (in Chinese)
• Wikipedia: Liu Wei Di Huang Wan
• Xiao’er Yao Zheng Zhi Jue (小兒藥證直訣), Rehmannia Pill — Zhongyi Jicheng (in Chinese)
• Korean Pharmacopoeia: Corni Fructus — Ministry of Food and Drug Safety (in Korean)
• Cornus Fruit (Chinese Pharmacopoeia 2020 monograph) — ShennongAlpha
• Dong et al. (2018), Corni Fructus: a review of chemical constituents and pharmacological activities — Chinese Medicine
• Czerwińska & Melzig (2018), Cornus mas and Cornus officinalis: analogies and differences of two medicinal plants — Frontiers in Pharmacology
• Gao et al. (2021), Active components and pharmacological effects of Cornus officinalis: literature review — Frontiers in Pharmacology
• Wikipedia: Loganin
• Plants of the World Online (Kew) — Cornus officinalis Siebold & Zucc.

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