Immature bitter orange

Chinese Name: Zhi shi
Medical Name: Fructus immaturus citri aurantii
Latin Name: Poncirus trifoliata, Citrus aurantium
Taste: Bitter

Quotes from Chinese historical sources

THE HERBAL CLASSIC OF SHEN-NONG: "The flavour is bitter and cold. It heals lesions of the skin, controls fevers and drives diseases from the body, provides relief from dysentery, and strengthens the muscles. It benefits the five internal organs."

OTHER CLASSIFIED RECORDS OF FAMOUS DOCTORS: "The flavor is sour, slightly cold, and not poisonous. Its main function is to eliminate masses in the chest, expel stale mucus, remove masses from the abdomen, and dispel distentions. It can also treat feelings of oppression in the epigastric region and pains arising from food retention; soothe stomach pains related to tension; treat fever-related pains in the ribs; break down stagnant qi in the stomach; provide relief from diarrhea and clear the eyes."

OPINIONS ON THE PROPERTIES OF HERBS: "A soup of bitter orange can expel accumulations of typhoid in the chest. Use it to treat bronchial asthma, damage to the kidney caused by disease, and in all cases where injury arises from stagnant energy. The flavour of the soup is bitter and pungent. It can cure nettle rashes, deficiencies in muscle arising from disease, chronic itching, haemorrhoids, infections of the digestive tract, stagnation of vital energy in the chest and abdomen, swellings of the ribs and diaphragm arising from consumptive disease. To prepare the root, simmer it in a shallow pan. Place a piece of the root in the mouth to cure toothache. Use it in cases of excess phlegm due to adverse energy."

RI HUA ZI MATERIA MEDICA: "Tonifies the spleen and strengthens the appetite; nourishes the five internal organs; prevents the rising of adverse energy; allays vomiting; dissipates phlegm; cures gastric disorders including nausea, cholera, dysentery and dyspepsia; dispels masses from the thorax and abdomen; harmonises the energies of the Five Organs, acts against colds, conjunctivitis, and fluid on the lungs; benefits large and small intestines; and relieves skin itching. In cases of swollen haemorrhoids, administer the herb after slow-frying with an adjuvant."

Western Research

Pharmazie. 2006 Sep;61(9):796-8.
Screening of potential chemopreventive compounds from Poncirus trifoliata Raf.
Pokharel YR, Jeong JE, Oh SJ, Kim SK, Woo ER, Kang KW.
College of Pharmacy, Chosun University, Gwangju, South Korea.
Chemopreventive agents induce a battery of genes whose protein products can protect cells from chemical-induced carcinogenesis. In this study, we isolated three different coumarins compounds (1; poncimarin, 2; heraclenol 3'-methyl ester and 3; oxypeucedanin methanolate) from Poncirus trifoliata Raf., and studied whether these compounds increase glutathione S-transferase (GST) expression and activity in the H4IIE cell-line. CDNB (1-chloro-2,4-dinitrobenzene; GST subtype-nonspecific) and NBD (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; GSTalpha-type-specific) assays revealed that compound 1 most potently increased GST enzyme activities. Western blot analysis using subtype-specific antibodies confirmed that these three coumarins also selectively increased GSTalpha-protein expression, and that compound 1 most actively induced GSTalpha. In contrast, the expressions of the GSTmu and GSTmu subtypes were not altered by these three coumarins. Reporter gene analysis using an antioxidant response element (ARE) containing construct and subcellular fractionation assays, revealed that GSTalpha-induction by compound 1 might be associated with Nrf2/ARE activation. These results suggest that these three coumarin compounds from Poncirus trifoliata Raf possess phase II enzyme inducible functions, and in particular, that poncimarin has chemopreventive potential.

Toxicol In Vitro. 2006 Oct;20(7):1071-6.
Anti-inflammatory effect of Poncirus trifoliata fruit through inhibition of NF-kappaB activation in mast cells.
Shin TY, Oh JM, Choi BJ, Park WH, Kim CH, Jun CD, Kim SH.
College of Pharmacy, Woosuk University, Jeonbuk 565-701, Republic of Korea.
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 with immune regulatory properties. We investigated the effect of the fruits of Poncirus trifoliata (L.) Raf (Rutaceae) (FPT) on expression of pro-inflammatory cytokines by activated human mast cell line, HMC-1. FPT dose dependently decreased the gene expression and production of TNF-alpha and IL-6 on phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated HMC-1 cells. In addition, FPT attenuated PMA and A23187-induced activation of NF-kappaB indicated by inhibition of degradation of I kappa B alpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that FPT might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

Clin Chim Acta. 2004 Feb;340(1-2):179-85.
Poncirus trifoliata fruit induces apoptosis in human promyelocytic leukemia cells.
Yi JM, Kim MS, Koo HN, Song BK, Yoo YH, Kim HM.
Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, 130-701 Seoul, South Korea.
BACKGROUND: Substances inducing apoptosis have shown efficacy in the treatment of cancers. Poncirus trifoliata (L.) Raf. (Rutaceae) fruits (PTF) has been used for the treatment of various cancers among Korean Oriental Medical doctors. METHODS: PTF-induced cytotoxicity of human leukemia HL-60 cells was monitored by the MTT assay. The apoptosis was determined by (a) apoptotic morphology in microscopy; (b) DNA fragmentation in electrophoresis and FACS analysis; and (c) activation of caspase-3 and poly-ADP-ribose polymerase (PARP) cleavage assay. RESULTS: The cytotoxic activity of PTF in HL-60 cells was increased in a concentration- and time-dependent manner. PTF caused the cell shrinkage, cell membrane blebbing, apoptotic body and DNA fragmentation. PTF-induced apoptosis is accompanied by the activation of caspase-3 and the specific proteolytic cleavage of PARP. However, PTF did not show cytotoxicity in normal peripheral blood mononuclear cells. CONCLUSIONS: Our novel finding provides evidence that PTF could be a candidate as an anti-leukemic agent through apoptosis of cancer cells.