Fumiko Konishi

Antitumor effect induced by a hot water extract of Chlorella vulgaris (CE): Resistance to meth-A tumor growth mediated by CE-induced polymorphonuclear leukocytes

SummaryWhen a hot water extract of Chlorella vulgaris (CE) was injected into the peritoneal cavity of BALB/c mice inoculated with syngeneic Meth-A tumor cells, the survival times were strikingly prolonged. Furthermore, peritoneal exudate cells (PEC) rich in polymorphonuclear cells (PMN) obtained from normal mice 24 h after CE injection exhibited an antitumor effect in a Winn-type assay using normal recipients. Such an activity of PEC remained almost intact after T cell or macrophage depletion. However, such PEC did not express an antitumor effect in a Winn-type assay using irradiated recipients. It was suggested that CE-induced PEC, presumably PMN, expressed an antitumor effect in cooperation with a host- or recipient-derived element(s) sensitive to irradiation. The anti-tumor mechanism of CE may be different from that of OK-432, one of the biological response modifiers.

Augmentation of antitumor resistance by a strain of unicellular green algae, Chlorella vulgaris

SummaryGrowth of Meth-A tumor in CDF1 mice was inhibited significantly by injection of a hot water extract of a strain of Chlorella vulgaris (CE) into the tumor or into the subcutaneous tissue near the tumor. The augmentation of resistance by CE may require the participation of T cells and macrophages, since it was abolished or reduced in athymic nude mice or mice treated with carrageenan, a macrophage blocker. Mice treated with CE exhibited antigen-specific augmented resistance against rechallenge with tumor. Moreover, the antitumor effect of CE was comparable with that of Corynebacterium parvum, but its mechanism of effect might be different.

Protective effect of an acidic glycoprotein obtained from culture of Chlorella vulgaris against myelosuppression by 5-fluorouracil

Abstract An acidic glycoprotein prepared from a culture of Chlorella vulgaris (CVS) was examined for its protective effect on 5-fluorouracil(5FU)-induced myelosuppression and indigenous infection in mice. Subcutaneous administration of CVS greatly reduced the mortality of non-tumor-bearing mice given a high dose of 5FU, and could increase the LD50 value of 5FU for these mice. After 5FU treatment, indigenous infection developed probably as a result of the impairment of the host defense system. CVS reduced the incidence of indigenous infections and this effect was attributable to the acceleration of recovery from 5FU-induced myelosuppression. Early recovery of hematopoietic stem cells, or cells responding to interleukin-3 or granulocyte/macrophage-colony-stimulating factor, was especially observed in the bone marrow of CVS-treated mice on days 4 – 9 after the injection of 5FU. When tumor-bearing mice were given CVS during treatment with 5FU, CVS prolonged the survival of mice without affecting the antitumor activity of 5FU. In addition, CVS was itself shown to exert an antitumor effect. These results suggested that CVS may be beneficial for the alleviation of side-effects in cancer chemotherapy without affecting the antitumor activity of the chemotherapeutic agent.

Enhanced resistance againstEscherichia coli infection by subcutaneous administration of the hot-water extract ofChlorella vulgaris in cyclophosphamide-treated mice

SummaryThe effects ofChlorella vulgaris extract (CVE-A) on the recovery of leukocyte number and the augmentation of resistance to bacterial infection were examined in CDF1 mice made neutropenic by cyclophosphamide (CY). They were treated intraperitoneally with CY (150 mg/kg) on day 0, and were given CVE-A (50 mg/kg) subcutaneously (s. c.) every other day from day 1 to day 13 after CY treatment. CVE-A accelerated the recovery of polymorphonuclear leukocytes (PMN) in the peripheral blood in CY-treated mice. The number of granulocyte/monocyte-progenitor cells (CFU-GM) in the spleen increased rapidly and highly after the administration of CVE-A in CY-treated mice, in contrast to the absence of change due to CVE-A in the number of bone marrow cells in CY-treated mice. Administration of CVE-A in CY-treated mice enhanced the accumulation of PMN in the inflammatory site and the activity of the accumulated leukocyte cells in luminol-dependent chemiluminescence. The mice became highly susceptible to an intraperitoneal infection withE.coli on day 4 after CY treatment, whereas the mice given CVE-A showed an enhanced resistance againstE.coli infection, irrespective of the timing of challenge. The bacterial number in CY-treated mice increased explosively after inoculation, resulting in death within 24 h. A progressive elimination of bacteria was observed from 6 h in the peritoneal cavity, spleen and liver of CY-treated mice given CVE-A s.c. These results indicate that CVE-A can be used as a potent stimulant of nonspecific resistance to infection in neutropenic mice.

Preventive effects of Chlorella on cognitive decline in age-dependent dementia model mice.

Oxidative stress is one of the major causes of age-dependent memory loss and cognitive decline. Cytotoxic aldehydes are derived from lipid peroxides and their accumulation may be responsible for age-dependent neurodegeneration, including Alzheimers disease. Since aldehyde dehydrogenases detoxify such aldehydes, we constructed transgenic mice with mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity deficiency (DAL101 mice) as an age-dependent dementia model. This model animal is age-dependently progressed by persistent oxidative stress, and thus enables us to investigate foods that prevent dementia. Since Chlorella, a kind of alga, exhibits various anti-oxidative effects, we investigated whether Chlorella has the potential to prevent age-dependent cognitive impairment. We fed Chlorella to DAL101 mice and investigated its effects on oxidative stress and the progression of cognitive decline using the Morris water-maze and object recognition tests. The diet with Chlorella tended to reduce oxidative stress and significantly prevented the decline of cognitive ability, as shown by both methods. Moreover, consumption of Chlorella decreased the number of activated astrocytes in the DAL101 brain. These findings suggest that the prolonged consumption of Chlorella has the potential to prevent the progression of cognitive impairment.

Oral Administration of Chlorella Vulgaris Augments Concomitant Antitumor Immunity

Chlorella vulgaris, an unicellular green algae, or its acetone-extract (Ac-Ex) were administered orally to Meth A tumor bearing BALB/c or (BALB/c x DBA/2)F1 (CDF1) mice. When CDF1 mice were fed daily with 10% dried powder of Chlorella vulgaris (CVP) containing diet before and after Meth A tumor inoculation, the growth of rechallenged Meth A tumor was significantly suppressed in an antigen-specific manner. Augmentation of antitumor resistance was exhibited also by Winn assay using lymph node cells of tumor-bearing mice orally administered with CVP or Ac-Ex. Antigen-specific concomitant immunity in these mice were mediated by cytostatic T cells but not by cytotoxic T cells. Natural killer cells seemed not to contribute in antitumor resistance in this system.

Anti-androgen effects of extracts and compounds from Ganoderma lucidum

The 30% EtOH extracts of Ganoderma lucidum Fr. Karst (Ganodermateceae) showed weak 5alpha-reductase inhibitory activity and binding ability to androgen receptor. When LNCaP (lymph-node carcinoma of the prostate) cells were treated with the EtOH extracts, cell proliferation was inhibited. Treatment with the extracts significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that G. lucidum might be a useful ingredient in the treatment of androgen-induced diseases, such as benign prostatic hyperplasia or prostate cancer. From the 30% EtOH extracts, we isolated ganoderiol F, which showed binding activity to androgen receptor and inhibited LNCaP cell proliferation, as one of the active compounds in the 30% EtOH extracts.

The effect of strain, growth stage, and cultivating condition of Ganoderma lucidum on 5α-reductase inhibition

The inhibitory effects of 102 methanol extracts of 40 mycelia, 9 culture fluids, and 53 fruiting bodies of 40 strains of Ganoderma lucidum on 5α-reductase were investigated. The methanol extract of the fruiting body of each strain was found to show the strongest 5α-reductase inhibitory activity among the extracts tested.

Estrogen-like activity of ethanol extract of Ganoderma lucidum

The ethanol extract from the fruiting body of Ganoderma lucidum was tested for its estrogen-like activity by using the cell proliferation assay (MCF-7 cells, human breast cancer cells), as well as the estrogen receptor binding assay, and pS2 mRNA expression assay in MCF-7 cells in vitro and uterotrophic assay in vivo. The ethanol extract of G. lucidum showed signifi cant positive effects on the proliferation of MCF-7 cells. This proliferation effect is related to the estrogenic activity of G. lucidum, because this proliferation activity was inhibited by the addition of the antiestrogenic compound ICI 182,780. The ability to bind to human estrogen receptors (hERs) α and β of the ethanol extract of G. lucidum was confi rmed by using the coactivator-bacterial alkaline phosphatase system. ER-dependent cell responsibilities were investigated by examining the regulation of gene transcription for pS2 in MCF-7 cells. Our results demonstrated that the pS2 mRNA levels are significantly increased by the ethanol extract of G. lucidum via an estrogen-like manner. Additionally, young rats that received the ethanol extract of G. lucidum (200 mg/kg per day) for 3 days showed a signifi cant increase (growth approximately twofold compared with the control group) in uterine weight after each treatment, which supports the estrogen-like activity of the ethanol extract of G. lucidum in vivo. It was concluded that the ethanol extract of G. lucidum showed estrogen-like activity, which may be useful in regulating hormone levels to treat related diseases such as osteoporosis if safety is fully guaranteed.

Immunopotentiating effects of a glycoprotein from chlorella vulgaris strain CK and its characteristics

Abstract Chlorella vulgaris strain CK, a unicellular greenalga, has been used as a health food for the past 30 years in Japan and in other countries. Oral administration of C. vulgaris results in several pharmacological effects, including augmenting host defenses in animal models and in human experiments. The oral administration of C. vulgaris showed clearprophylactic effects in stress-induced peptic ulcer models, presumably through the “immune-brain-gut” axis, and it also suppressed a Meth A tumor growth in an antigen-specific manner. C. vulgaris in active form, known as CVS, was purified from the culture supernatant of C. vulgaris and found to be a glycoprotein with a molecular weight of 63,100 amu. CVS contains 67% carbohydrate with a β-l,6-D-galactopyranose backbone and 35% protein. A protein moiety is essential for CVS to exhibit immunopotentiating activity, and 15-mer of the partial amino acid sequence at the NH2-terminus has been determined. CVS exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis by intratumor (i.t.) injection. Prophylactic effects of CVS were observed on 5-fluorouracil-induced myelosuppression and indigenous infection by subcutaneous injections. From these results, it became evident that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and accelerates recruitment of these cells to the tumorsites. Presurgical treatment with CVS might prevent metastasis and/or the progression of residual tumors. CVS may also be beneficial for the alleviation of adverse effects of cancer chemotherapy, causing an early recovery of hematopoietic stem cells without affecting the antitumor activity of chemo-therapeutic agents.