CC1 – Cervical Cancer

Chai Hu –Radix Bupleuri

1. Cytokine production by human lymphocytes stimulated by a herbal compound containing Bupleurum (KY88 LIVER LIVO).
AIM: Compounds containing Bupleurum possess immunomodulating effects. KY88 LIVER LIVO (KY88) is a blend of such compound. The aim of this study is to investigate the effects of KY88 on the production of cytokines by lymphocytes in vitro. METHODS: Seventy Sprague Dawley rats were used of which 40 were orally fed with 4 mg purified KY88 for 35 d. Normal human lymphocytes were isolated and cultured in standard conditions. The culture medium was collected at zero and 72 h after the KY88 treatment. The cytokines, including interleukin-1beta (IL-1beta), IL-2, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma, were measured by ELISA kits. RESULTS: TNF-alpha levels in the supernatant of cultured human lymphocytes significantly increased after the treatment of PHA and KY88. The mean levels were (855+/-251), (399+/-145), and (176+/-49) ng/L after the treatment with KY88 at the concentrations of 10, 1 and 0.1 g/mL respectively. However, the level in the control group without specific treatment was only (68+/-4) ng/L. The difference between KY88 10 g/mL and control groups was significant (P<0.05). KY88 may regulate the immune function through the induction of TNF-alpha expression.
––Chow WC, Loo TY, Sham ST. Acta Pharmacol Sin. 2003 Feb;24(2):140-4. 

2. Inhibitory effect of bupleuri radix saponins on adhesion of some solid tumor cells and relation to hemolytic action: screening of 232 herbal drugs for anti-cell adhesion.
Among 232 herbal drugs tested, six showed a remarkable anti-cell adhesive activity, and the extract from the roots of Bupleurum falcatum (Umbelliferae), the semen of Psorala corylifolia (Leguminosae), and the semen of Areca catechu (Palmae) showed an anti-cell adhesive action at non-cytotoxic concentrations. Saikosaponins-a, d and e, isolated from the roots of Bupleurum falcatum, exhibited a potent anti-cell adhesive activity and a strong hemolytic action. In a structure-activity relationship for both activities, it seems that a sugar moiety and an ether linkage between C-13 and C-28 are required for good bioactivities. In addition, saikosaponin d with a beta-hydroxy group at C-16 was more potent than saikosaponin a possessing an alpha-hydroxy group. Taken together, it is suggested that the mechanism for anti-cell adhesive activity of saikosaponin may resemble that for their hemolytic action.
––Ahn BZ, Yoon YD, Lee YH, Kim BH, Sok DE. Planta Med. 1998 Apr;64(3):220-4. 

3. Induction of differentiation in rat C6 glioma cells with Saikosaponins.
The effects of saikosaponins (a, b(1), b(2), c, d), isolated from Bupleurum Radix, on the induction of differentiation in rat C6 glioma cells were studied. Saikosaponins a and d were shown to inhibit cell proliferation and alter cell morphology. In addition to cytostasis, the enzymatic activities of glutamine synthetase (GS) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were also noticeably increased after treatment with saikosaponin a. Nevertheless, saikosaponin d only showed an increase of GS activity, no significant changes in CNP activity were found. These results suggest that saikosaponin a can induce the differentiation of C6 glioma cells into astrocytes and/or oligodendrocytes, but saikosaponin d can only induce the differentiation of C6 glioma cells into astrocytes.
––Tsai YJ, Chen IL, Horng LY, Wu RT. Phytother Res. 2002 Mar;16(2):117-21.


Tu Fu Ling – Rhizoma Smilacis

1. Studies on the chemical constituents of Smilax glabra
Smilax glabra is a well-known traditional Chinese medicine which has been used clinically to prevent leptospirosis, to treat syphilis, and acute bacterial dysentery, etc. Its extracts showed anti-tumor and anti-atherosclerosis activity. A new isoflavone, 7,6'-dihydroxy 3'-methoxy isoflavone (1), along with two known compounds taxifolin (2) and astilbin (3), have been isolated from the roots of Smilax glabra. The structures were elucidated by spectroscopic methods including 2DNMR techniques.
––Yi Y, Cao Z, Yang D, Cao Y, Wu Y, Zhao S. Yao Xue Xue Bao. 1998 Nov;33(11):873-5. 

2. Anticancer effect
This herb had certain inhibitory effect on rat liver cancer induced by AFB1, it also had inhibitory effect on transplanted tumors.

Jin Yin Hua – Flos Lonicerae

1. Anticancer effect
In vitro experiments showed that water and wine immersion fluid of jin yin hua had obvious cytoxic effect on Sarcoma 180 and Ehrlich carcinoma.

2. Clinical study
Jin Yin Hua Lu, 100ml, tid, 2 weeks as a course of treatment, analyze the effect after 2 courses. 978 cases of thirsty caused by radiotherapy and chemotherapy in tumor treatment were treated, the effective rate was 87% in radiotherapy group, and 74% in chemotherapy group.

Zhu Ling – Sclerotium Polypori

1. Combined effects of chuling (Polyporus umbellatus) extract and mitomycin C on experimental liver cancer.
Chuling (Polyporus umbellatus), one of the commonly used Chinese medical herbs, was combined with mitomycin C and then studied against intrahepatic implantation of sarcoma 180 tumor cells in mice. Oral administration of chuling extract, intraperitoneal injection of mitomycin C and the combination of both increased the life span of tumor-bearing mice 71.6%, 70.1% and 119.9%, respectively. The same treatments were found to be cytotoxic to Sarcoma-180-induced liver tumor cells. The synthetic rates of DNA, RNA and protein were all inhibited measurably by the combined treatment. Histopathological studies showed that lymphocytes infiltrated and surrounded the cancer cells, and there was some fibrosis found in normal cells and cancer cells. These results indicate the potential use of chuling as an anticancer agent.
––You JS, Hau DM, Chen KT, Huang HF. Am J Chin Med. 1994;22(1):19-28. 

2. Studies on constituents of fruit body of Polyporus umbellatus and their cytotoxic activity.
From the crude drug Chorei, the fruit body of Polyporus umbellatus, seven new components named polyporusterone A, B, C, D, E, F and G, were isolated and their structures were determined on the basis of the spectral data. These compounds showed cytotoxic action on leukemia 1210 cell proliferation.
––Ohsawa T, Yukawa M, Takao C, Murayama M, Bando H. Chem Pharm Bull (Tokyo). 1992 Jan;40(1):143-7.  

3. Anti-tumor effect
Polysaccharide of zhu ling had anticancer effect. Intraperitoneal injection of water soluble part of ethanol extract of zhu ling at the dosage of 2g (crude drug)/kg daily for consecutive 10 days had an inhibitory rate of 62% on Sarcoma180 in mice, and 37~54% on liver cancer of mice. But it had no effects on mice leukemia L615..

4. Clinical study
zhu ling extract 757 was used to treat lung cancer and oesophagus cancer and it’s believed preliminarily that it had anti-tumor effects and could improve immune function.

Ze Xie – Rhizome Alisma orientalis

No related research.


Bai Mao Gen – Rhizoma Imperatae

1. Cylindol A, a novel biphenyl ether with 5-lipoxygenase inhibitory activity, and a related compound from Imperata Cylindrica.
Cylindol A [1] and B [2], two novel substances, have been isolated from Imperata cylindrica, and their structures have been elucidated on the basis of their spectral data coupled with chemical evidence and total synthesis. Cylindol A [1] showed 5-lipoxygenase inhibitory activity.
––Matsunaga K, Ikeda M, Shibuya M, Ohizumi Y. J Nat Prod. 1994 Sep;57(9):1290-3. 


Che Qian Zi – Semen Plantaginis

1. In vitro anti-hepatoma activity of fifteen natural medicines from Canada.
Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae), Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae), Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent. (Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L. (Malvaceae), which have been used as folk medicine in Canada, were evaluated for their anti-hepatoma activity on five human liver-cancer cell lines, i.e. HepG2/C3A, SK-HEP-1, HA22T/VGH, Hep3B and PLC/PRF/5. The samples were examined by in vitro evaluation for their cytotoxicity. The results showed that the effects of crude drugs on hepatitis B virus genome-containing cell lines were different from those against non hepatitis B virus genome-containing cell lines. C. groenlandica was observed to be the most effective against the growth of all five cell lines and its chemotherapeutic values will be of interest for further studies.
––Lin LT, Liu LT, Chiang LC, Lin CC. Phytother Res. 2002 Aug;16(5):440-4.


Gui Wei (Dang Gui) – Extremitas Radix Angelica

1. Experimental study on effect of Angelica polysaccharide in inhibitory proliferation and inducing differentiation of K562 cells
OBJECTIVE: To investigate the application value of Angelica polysaccharide (APS) on proliferation and differentiation of human erythroleukemia K562 cells. METHODS: The effect of APS in inhibitory proliferation and inducing differentiation of human erythroleukemia K562 cells was studied by modern experimental hematologic techniques such as cell counting and culture, flowcytometry, morphology, cytochemistry and cell differential immune phenotyping. RESULTS: APS could significantly inhibit the proliferation of K562 cells in vitro and prevent the cell from entering the active proliferative phase (P < 0.05). After being induced by APS, the differentiation of K562 cells to erythrocyte series and granulo-monocyte series increased, positive rate of benzidine, glycogen and peroxidase stain elevated, and cell surface differential antigen CD15 expression promoted significantly (P < 0.05), while C-MYC expression of K562 cells induced by APS induction lowered significantly (P < 0.05). CONCLUSION: APS could not only inhibit the proliferation of K562 cells in vitro, but also induce the differentiation of K562 cells toward erythrocyte and granulocyte series. It may be a natural inducer with promising prospect of development and application.
––Zheng M, Wang YP. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002 Jan;22(1):54-7.  

2. Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis.
A low molecular weight polysaccharide has been isolated from the rhizome of Angelica sinensis (Oliv.) Diels (Umbelliferaer). It has a molecular weight of approximately 3,000 and consists of protein (4.73%) and carbohydrate (85.85%) of which 5.2% is uronic acid. It shows strong anti-tumor activity on Ehrlich Ascites tumor bearing mice. It also exhibits immunostimulating activities, both in vitro and in vivo.
––Choy YM, Leung KN, Cho CS, Wong CK, Pang PK. Am J Chin Med. 1994;22(2):137-45.

3. Clinical Studay
Hua Liu Tang: dang gui wei, 10g; chi shao, 10g; hong hua 10g; tao ren 10g; dan shen 20g; shu zhi 10g; ban zhi lian 30g; bai hua she she cao 30g, 5 cases of brain tumor were treated for 6 months, and they survived for 2~7 years. Among 28 cases of thyrophyma, all were effective except for 3 cases.

Chi Shao – Radix Rubrus Paeonia

1. Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway.
Paeoniae Radix (PR) is the root of traditional Chinese Herb named Paeonia lactiflora Pallas, which is commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that PR has anticancer growth activities, however the mechanism underlying these activities was unclear and remained to be elucidated. In this study, we evaluated the molecular mechanism of the effect of PR on human hepatoma cell lines, HepG2 and Hep3B. Our results showed that the water-extract of Paeoniae Radix (PRE) had inhibitory effect on the growth of both HepG2 and Hep3B cell lines. The induction of internucleosomal DNA fragmentation and chromatin condensation appearance, and accumulation of sub-G1 phase of cell cycle profile in PRE treated hepatoma cells evidenced that the cytotoxicity of PRE to the hepatoma cells is through activation of the cell death program, apoptosis. The activation of apoptosis by PRE is independent of the p53 pathway as Hep3B cell is p53-deficient. In addition, the differential gene expression of PRE treated HepG2 was examined by cDNA microarray technology and RT-PCR analysis. We found that the gene expression of BNIP3 was up-regulated while ZK1, RAD23B, and HSPD1 were down-regulated during early apoptosis of the hepatoma cell mediated by PRE. The elucidation of the drug targets of PR on inhibition of tumor cells growth should enable further development of PR for liver cancer therapy.
––Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Waye MM. Life Sci. 2002 Sep 27;71(19):2267-77. 

2. Effects on tumors
Intraperitoneal injection of normal butyl alcohol extract of chi shao at the dosage of 1~1.5g/kg had obvious inhibitory effect on S180 solid tumor. Combination of water extract of chi shao and cyclophosphane or amethopterin had obvious effect on the growth of S180 solid tumor and survival time of L615 mice.  There’re also reports showing that water extracts could promote the formation of ascites in Ehrlich carcinoma. S180 and W256 ascites carcinoma and significantly shorten the survival time.