1. Isolation of two cytotoxic diterpenes from the fern Pteris multifida.
From aerial parts of the fern Pteris multifida Poir. (Polypodiaceae) two diterpenes, entkaurane-2 beta, 16 alpha-diol and ent-kaur-16-ene-2 beta, 15 alpha-diol, were isolated by repeated column chromatography using silica gel and silica gel impregnated with silver nitrate. The structures were confirmed by spectroscopic methods. Both compounds showed a moderate cytotoxicity to Ehrlich ascites tumour cells.
––Woerdenbag HJ, Lutke LR, Bos R, Stevens JF, Hulst R, Kruizinga WH, Zhu YP, Elema ET, Hendriks H, van Uden W, Pras N. Z Naturforsch [C]. 1996 Sep-Oct;51(9-10):635-8.
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.
1. Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas.
Kuei-chih-fu-ling-wan (Keishi-bukuryo-gan; KBG), a traditional Chinese herbal remedy contains five components: bark of Cinnamomum cassia Bl. (Lauraceae), root of Paeonia lactiflora Pall. (Paeoniaceae), seed of Prunus persica Batsch. or P. persiba Batsch.var.davidiana Maxim. (Rosaceae), carpophores of Poria cocos Wolf. (Polyporaceae), and root bark of Paeonia suffruticosa Andr. (Paeoniaceae). This prescription has been frequently used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and sterility. We previously reported that KBG might act as a LH-RH antagonist and a weak anti-estrogen on the uterine DNA synthesis in immature rats. In the present study, we investigated the effects of KBG on 110 premenopausal patients with uterine myomas. Clinical symptoms of hypermenorrhea and dysmenorrhea were improved in more than 90% of the cases with shrinking of uterine myomas in roughly 60% of the cases.
––Sakamoto S, Yoshino H, Shirahata Y, Shimodairo K, Okamoto R. Am J Chin Med. 1992;20(3-4):313-7.
2. Anti-tumor Promoting Effect of Glycosides from Prunus persica Seeds.
Four minor components, along with the major cyanogenic glycosides, amygdalin and prunasin, were isolated from Prunus persica seeds (Persicae Semen; Tounin), and characterized as mandelic acid glycosides (beta-gentiobioside and beta-D-glucoside) and benzyl alcohol glycosides (beta-gentiobioside and beta-D-glucoside). The anti-tumor promoting activity of these compounds was examined in both in vitro and in vivo assays. All of the compounds significantly inhibited the Epstein-Barr virus early antigen activation induced by tumor promoter. In addition, they produced a delay of two-stage carcinogenesis on mouse skin that was comparable in potency to (-)-epigallocatechin gallate from green tea. Structure-activity relationships indicated that a substituent at the benzylic position with glycosidic linkage affected the in vitro and in vivo activities with an order of enhancing potency, CN<COOH<H.
––Fukuda T, Ito H, Mukainaka T, Tokuda H, Nishino H, Yoshida T. Biol Pharm Bull. 2003 Feb;26(2):271-3.
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. Pharmacotherapeutic effects of kuei-chih-fu-ling-wan (keishi-bukuryo-gan) on human uterine myomas.
Kuei-chih-fu-ling-wan (Keishi-bukuryo-gan; KBG), a traditional Chinese herbal remedy (Gui Zhi Fu Ling Wan) contains five components: bark of Cinnamomum cassia Bl. (Lauraceae), root of Paeonia lactiflora Pall. (Paeoniaceae), seed of Prunus persica Batsch. or P. persiba Batsch.var.davidiana Maxim. (Rosaceae), carpophores of Poria cocos Wolf. (Polyporaceae), and root bark of Paeonia suffruticosa Andr. (Paeoniaceae). This prescription has been frequently used in the treatment of gynecological disorders such as hypermenorrhea, dysmenorrhea and sterility. We previously reported that KBG might act as a LH-RH antagonist and a weak anti-estrogen on the uterine DNA synthesis in immature rats. In the present study, we investigated the effects of KBG on 110 premenopausal patients with uterine myomas. Clinical symptoms of hypermenorrhea and dysmenorrhea were improved in more than 90% of the cases with shrinking of uterine myomas in roughly 60% of the cases.
––Sakamoto S, Yoshino H, Shirahata Y, Shimodairo K, Okamoto R. Am J Chin Med. 1992;20(3-4):313-7.
1. Treatment of intestinal metaplasia and atypical hyperplasia of gastric mucosa with xiao wei yan powder
138 cases of intestinal metaplasia (IM) and 104 cases of atypical hyperplasia (AH) of the gastric mucosa of chronic gastritis treated with Xiao Wei Yan Powder (XWYP) were reported. The diagnoses were based on the pathological examination of gastric antrum biopsy specimens. The cases were randomly divided into treated group and control group. The XWYP contained Smilax glabrae, Hedyotis diffusae, Taraxacum mongolicum, Caesalpinia sappan, Paeonia alba, Cyperus rotundus, Bletilla striata, Glycyrrhiza uralensis etc., and was prepared in powder form, taken orally 5-7g tid. After 2-4 months of administration, gastroscopic and pathological examinations were repeated. Results: In treated group, the total effective rate of IM was 91.3% and that of the AH was 92.16%, while in control group, they were 21.3% and 14.46% respectively (P < 0.01). It denoated that XWYP had marked therapeutic effects for IM and AH. The animal experiments revealed no toxic effect, so safety guarantee was provided for its clinical application.
––Liu XR, Han WQ, Sun DR. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992 Oct;12(10):602-3, 580.
1. The variable effect on proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin.
OBJECTIVE: Naringenin, a naturally occurring flavonoid found in citrus fruits, is known to have anticarcinogenic properties. We have examined the effect of Naringenin on cell proliferation of an HT-29 colon cancer cell line. METHODS: HT-29 colon cancer cells were cultured in 96-well tissue culture plates. Naringenin concentrations ranging from 0.02 to 2.85 mmol were added to the wells of the Test group. The Control group contained all the elements present in the Test group with the exception of Naringenin. Cell proliferation was measured by colourimetric assay using the 2% WST-1 cell proliferation kit. RESULTS: Significant inhibition of cell proliferation was observed in HT29 colon cancer cells exposed to Naringenin at doses greater than 0.71 mmol. CONCLUSIONS: These results suggest a potential role for citrus fruits as a source of chemoprotective agents for colon cancer.
––Frydoonfar HR, McGrath DR, Spigelman AD. Colorectal Dis. 2003 Mar;5(2):149-52.
2. Antiproliferative activities of citrus flavonoids against six human cancer cell lines.
Citrus fruits contain high concentrations of several classes of phenols, including numerous hydroxycinnamates, flavonoid glycosides, and polymethoxylated flavones. The latter group of compounds occurs without glycosidic linkages and has been shown to inhibit the proliferation of a number of cancer cell lines. This antiproliferative property was further demonstrated against additional human cancer cell lines, and the antiproliferative actions of a series of synthetic methoxylated flavones were also studied. Similar to the naturally occurring compounds, the synthetic compounds exhibited strong antiproliferative activities. In many cases the IC(50) values occurred below 10 microm. Other hydroxylated flavone and flavanone aglycons also exhibited antiproliferative activities against the cancer cell lines, with the flavones showing greater activities than the flavanones. Glycosylation of these compounds removed their activity. The strong antiproliferative activities of the polymethoxylated flavones suggest that they may have use as anticancer agents in humans.
––Manthey JA, Guthrie N. J Agric Food Chem. 2002 Oct 9;50(21):5837-43.
3. Anticancer and health protective properties of citrus fruit components.
Accumulated evidence from experimental and epidemiological studies indicates that there is a low risk of degenerative diseases, cardiovascular disease, hypertension, cataract, stroke and, in particular, cancers in people with a high intake of fruit and vegetables. This protective effect is assumed to be associated mainly with the antioxidant activities of either individual or interacting bioactive components present in the fruits and vegetables, and with other biochemical and physical characteristics of the identified and unknown bioactive components. The implicated bioactive components present in citrus fruits include vitamin C, beta-carotene, flavonoids, limonoids, folic acid, and dietary fibre. A high intake of citrus fruits may reduce the risk of degenerative diseases.
––Silalahi J. Asia Pac J Clin Nutr. 2002;11(1):79-84.
1. Corosolic acid isolated from the fruit of Crataegus pinnatifida var. psilosa is a protein kinase C inhibitor as well as a cytotoxic agent.
Corosolic acid isolated from the fruit of Cratoegus pinnatifida var. psilosa was tested for anticancer activity. Corosolic acid displayed about the same potent cytotoxic activity as ursolic acid against several human cancer cell lines. In addition, the compound displayed antagonistic activity against the phorbol ester-induced morphological modification of K-562 leukemic cells, indicating the suppression of protein kinase C (PKC) activity by the cytotoxic compound. The compound showed PKC inhibition with dose-dependent pattern in an in vitro PKC assay.
––Ahn KS, Hahm MS, Park EJ, Lee HK, Kim IH. Planta Med. 1998 Jun;64(5):468-70.
2. Cytotoxic triterpenes from Crataegus pinnatifida.
Bioassay-guided fractionation of Crataegus pinnatifida (Rosaceae) gave two cytotoxic ursane-type triterpenes which were identified as uvaol (1) and ursolic acid (2) by physicochemical and spectroscopic methods. 3-Oxo-ursolic acid (3) was synthesized from ursolic acid (2) by Jones method. The cytotoxic activities of these compounds were tested against murine L1210 and human cancer cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) in vitro. Compounds 1 and 2 showed moderate cytotoxicities against L1210, whereas they showed weak activities against human cancer cell lines. However, compound 3 exhibited potent cytotoxic activities both in murine and in human cancer cell lines.
––Min BS, Kim YH, Lee SM, Jung HJ, Lee JS, Na MK, Lee CO, Lee JP, Bae K. Arch Pharm Res. 2000 Apr;23(2):155-8.
1. Clinical study
xia ku cao was used as the main herb, and combined with yin chen, bai hua she she cao, hai zao, kun bu, lou lu. The formula was used to treat primary liver cancer and had certain therapeutic effect.
1. Stimulating activity of Chinese medicinal herbs on human lymphocytes in vitro.
The effects of eight kinds of Chinese medicinal herbs (CMH) on human lymphocytes was studied in vitro. The extract of Cinnamomum cassia presl markedly stimulated human lymphocytes to proliferate. Codonopsis pilosula, Oldenlandia diffusa and Rhizoma typhonii weakly stimulated. These extracts enhanced cytotoxic T-lymphocyte (CTL) activity, but failed to enhance natural killer (NK)-cell activity. The extracts of these CMHs have stimulatory effect on immunoglobulin (Ig) production by B-cells and interleukin(IL)-1 production by monocytes. These activities of Cinnamomun cassia presl extract are associated with glycoproteins, whose molecular weight was about 100 KDa. These results suggest that CMH extracts have a stimulating activity on human lymphocytes and these abilities could be used clinically for the treatment of diseases such as cancer.
––Shan BE, Yoshida Y, Sugiura T, Yamashita U. Int J Immunopharmacol. 1999 Mar;21(3):149-59.
2. Immunological and hematopoietic effect of Codonopsis pilosula on cancer patients during radiotherapy]
Codonopsis pilosula was used as an adjuvant in 76 cancer patients during radiotherapy and its protective effect on hematopoietic and immunologic function was studied. Results: (1) No influence on Hb and WBC of the patients with radiotherapy. (2) It could reduce the immunosuppressive effect of radiotherapy on delayed hypersensitive reaction, the lymphocyte response to PHA and IL-2. (3) No difference between treated and control groups in most humoral immune indices such as IgG, IgA and C3, but had slight increase in IgM in treated patients, while significant decrease in control.
––Zneg XL, Li XA, Zhang BY. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992 Oct;12(10):607-8, 581.
1. The in vitro potentiation of LAK cell cytotoxicity in cancer and aids patients induced by F3--a fractionated extract of Astragalus membranaceus
The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno-regulatory component of Astragalus membranaceus was shown capable of potentiating the LAK cell inducing activity of rIL-2. The killing activity against Hs294T melanoma cell line of LAK cells induced by 50 U/ml rIL-2 in the presence of F3 (55 micrograms/ml) reached 64% which was comparable to that (60%) induced by 500 u/ml of rIL-2 alone. With F3 plus rIL-2, the effector to target cell ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity when rIL-2 was used alone. In some patients, whose peripheral blood lymphocytes were relatively inert to rIL-2, F3 could make them responsive to rIL-2. These results imply that F3 may be useful to potentiate LAK cell activity, reduce the amount of rIL-2 and thus minimize the later's toxic side effects when used in vivo.
––Chu DT, Lin JR, Wong W. Zhonghua Zhong Liu Za Zhi. 1994 May;16(3):167-71.
2. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats.
Astragalus membranaceus (AM) has been widely used for treating liver diseases in traditional Chinese medicine. Experimental evidence indicates that it has antitumor potential. In this study, the effect of AM on hepatocarcinogenesis induced by diethylnitrosamine (DEN), two-thirds partial hepatectomy, and 2-acetylaminofluorene (2-AAF) (DEN-PH-AAF) was evaluated using glutathione S-transferase placenta form (GST-P) as marker. First, rats were injected intraperitoneally (i.p.) with DEN (200 mg/kg in saline), a two-thirds partial hepatectomy was carried out 2 weeks later, and the rats were then placed on a basal diet containing 0.02% AAF from week 3 to week 8 to induce hepatocarcinogenesis. The rats were given AM (90 mg/kg or 180 mg/kg body weight) by gavage from week 3 to week 8 (treatment groups). The formation of GST-P-positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF were reduced in the treatment groups, which clearly suggests that AM is effective in delaying DEN-PH-AAF-induced hepatocarcinogenesis.
––Cui R, He J, Wang B, Zhang F, Chen G, Yin S, Shen H. Cancer Chemother Pharmacol. 2003 Jan;51(1):75-80. Epub 2002 Nov 26.
3. Effect of Astragalan on secretion of tumor necrosis factors in human peripheral blood mononuclear cells
The extracts of Astragalus membranaceus have been further isolated by liquid chromatography. One of the fractions (Astragalan, M.W. 20,000-25,000) could enhance the secretion of tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMC) in vitro. After isolation of adherent and nonadherent mononuclear cells from PBMC, Astragalan increased the secretion of TNF-alpha and TNF-beta respectively. These results suggest further study of Astragalan would promote the application of Astragalan in cancer immunotherapy.
––Zhao KW, Kong HY. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993 May;13(5):263-5, 259.