The Antitumor, Anti-inflammatory and Analgesic Effects of Sichuan Pepper (Huajiao)

Huajiao (Sichuan pepper) is the dried ripe fruit of the Rutaceae plants Zhujiao (Zanthoxylum schinifolium) or Huajiao (Zanthoxylum bungeanum). It contains volatile oil, terpenoids, amino acids, minerals and protein. The volatile oil of Sichuan pepper is the main source of its aroma, and contains chiefly linalool, linalyl propionate, limonene, anethole, fagaronine (xanthoxylin) and 4-terpineol.

TCM holds that Sichuan pepper is acrid and warm in nature, enters the Spleen, Stomach and Kidney meridians, and has a mild toxicity. It has the actions of warming the middle and stopping pain, and killing parasites to relieve itching. Raw Sichuan pepper has a mild toxicity; for external use it kills parasites and stops itching, and is used for scabies, eczema or skin pruritus.

Modern pharmacological studies show that both the volatile oil and the extracts of Sichuan pepper have antitumor effects. The volatile oil is cytotoxic to pheochromocytoma cells: at a concentration above 2 mg/ml it causes marked injury to PC-12 cells, and above 0.5 mg/ml it inhibits the growth of PC-12 cells. This indicates that Sichuan pepper can inhibit PC-12 cells and possesses anti-pheochromocytoma activity.

Treating H22 cells with 4 mg/ml Sichuan pepper volatile oil for 72 hours significantly inhibits the proliferation of H22 cells. Treating H22 cells with 1 mg/ml volatile oil for 72 hours already produces a sub-apoptotic peak. Animal experiments show that the volatile oil significantly inhibits the growth of solid tumors in mice; it inhibits the proliferation of H22 hepatoma cells and induces apoptosis, but it does not exert its antitumor effect by enhancing immune function. At 4-16 mg/ml the volatile oil is cytotoxic to human lung cancer A549 cells, with an inhibition rate reaching 87.19%; at 1 mg/ml it induces apoptosis in A549 cells, with an inhibition rate of 40.12%.

A study on the effect of Sichuan pepper volatile oil against cervical cancer Hela cells showed that treating HeLa cells with 4 mg/ml volatile oil for 72 hours significantly inhibits proliferation and induces apoptosis; treating HeLa cells with 1 mg/ml volatile oil for 72 hours also inhibits proliferation and induces apoptosis. The volatile oil also markedly inhibits the proliferation of human cervical cancer CaSki cells, and this inhibition increases with both drug concentration and duration of action. At a volatile oil concentration of 4 mg/ml, the inhibition rate was 20% at 24 hours, 46% at 49 hours, and 78% at 72 hours.

In addition, Sichuan pepper extracts at various concentrations also have antitumor effects. Extracts at all tested concentrations inhibited the proliferation of SGC7901 cells, and the growth-inhibiting effect increased with concentration, showing a concentration-effect relationship. At a concentration of 2 mg/ml or above, the inhibition of cell proliferation was markedly enhanced; at 4 mg/ml the inhibition was near its maximum, reaching 88.4%. Meanwhile, the effect also grew with the duration of exposure: 48 hours was greater than 24 hours, and 72 hours was markedly greater than 24 hours. In its effect against human gastric cancer SGC-7901 cells, the drug's efficacy was both concentration- and time-dependent. Promoting apoptosis of gastric cancer SGC-7901 cells is one of the main pathways by which the extract inhibits tumor-cell proliferation and growth.

The volatile oil and the water-soluble fraction of Sichuan pepper also have relatively strong anti-inflammatory, analgesic and anesthetic effects. However, when Sichuan pepper is combined with reserpine its analgesic effect disappears, and when combined with phentolamine its analgesic effect is weakened. Propranolol has no effect on its analgesic action. The skimmianine contained in Sichuan pepper may be one of its active analgesic components.

(The above data are adapted from Antitumor Chinese Materia Medica: Pharmacology and Clinic, edited by Ji Yubin.)

In TCM, Sichuan pepper is also called Shujiao, Dajiao, Qinjiao, Bajiao and Hanjiao. The earliest TCM materia medica, the Shennong Bencao Jing (Divine Farmer's Classic of Materia Medica), already included this herb. It records: "Qinjiao (Sichuan pepper) mainly expels wind-evil, warms the middle, removes cold-bi, strengthens the teeth and hair, and brightens the eyes. Taken over a long time it lightens the body, improves complexion, resists aging, prolongs life and opens spiritual understanding." There are many records of Sichuan pepper being used to treat tumor-accumulation type diseases. For example, the Rihuazi Bencao records: "Shujiao breaks concretions and gatherings, opens the stomach, treats seasonal epidemics and warm diseases, postpartum retained blood, and qi in the heart and abdomen."

The Jingui Yaolue (Essential Prescriptions of the Golden Coffer) by the Han-dynasty physician Zhang Zhongjing uses Sichuan pepper in Da Jianzhong Tang: "It treats great cold pain in the chest and abdomen, vomiting with inability to eat, cold in the abdomen rushing upward so that ridges rise under the skin showing head and feet, with pain above and below that cannot be touched. Use Shujiao two ge (dry-fried to remove sweat), dried ginger four liang, ginseng two liang. Decoct in water, strain, add one sheng of yitang (malt sugar), simmer over low heat, divide and take warm in two doses; after about the time it takes to cook a meal, two sheng of gruel may be drunk."

Sichuan pepper is often used to treat abdominal fullness, chest and abdominal pain, incessant watery diarrhea, cold-hernia abdominal pain, toothache, mouth ulcers, chapped hands and feet, bald sores, and chilblains. It can also be used to stop lactation. In modern times it has been found useful for biliary ascariasis, psoriasis, fungal vaginitis and stubborn tinea.

The root, leaves and stem of Sichuan pepper can all be used as medicine, and their actions are basically similar to those of the pericarp.

(The above content is adapted from the Zhongyao Da Cidian (Dictionary of Chinese Materia Medica).)