Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation.

Int J Gynecol Cancer. 2009 Dec;19(9):1564-9

Authors: Kamath SG, Chen N, Xiong Y, Wenham R, Apte S, Humphrey M, Cragun J, Lancaster JM

The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways.

BOTTOM LINE: Gedunin is a “tetranortriterpenoid” isolated from the Indian neem tree (Azadirachta indica),  and has shown anticancer activity recently against several cancer cell lines in the lab.  In this case, the study shows that it may be effective against ovarian cancer and help one of the main ovarian cancer chemotherapy drugs (cisplatin) work better.  Remember, the main drug we use against ovarian cancer today (Taxol) was derived from a ewe tree.  Another, currently being studied, is from a sea squirt.  So, no question that the anti-cancer war is not just a synthetic pharmaceutical battle.  In fact, the anti cancer war is right in the middle of many natural substances that potentially will help us win this “war”.  The difference is that the “natural” front is attacking BOTH the anticancer cell attack strategy and strengthening the body from which cancer cells need to be driven from…….or prevented from gaining a foothold in the first place.

Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia.

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 27;

Authors: Kawanabe T, Yoritaka A, Shimura H, Oizumi H, Tanaka S, Hattori N

OBJECTIVE: To evaluate the efficacy and safety of Yokukansan, a traditional Chinese herbal medicine, for treating of behavioral and psychological symptoms of dementia (BPSD) in patients with Parkinson disease (PD;n=7) and those with PD with dementia (PDD;n=7). BACKGROUND: BPSD are often seen in patients with senile dementia and have serious deleterious effects on the lives of patients and caregivers. Recent studies indicate that the traditional Chinese herbal medicine Yokukansan may be safe and beneficial for the treatment of BPSD patients. METHODS: We treated 7 PD and 7 PDD patients for 4weeks with Yokukansan and observed them without Yokukansan for 4weeks. Changes in behavioral and psychological symptoms were evaluated every 4weeks according to the Neuropsychiatric Inventory (NPI) scale. RESULTS: Significant improvements in behavioral and psychological symptoms, particularly in the incidence and duration of hallucinations, were observed in most PD and PDD patients after 4weeks of Yokukansan treatment. No significant changes were observed in the laboratory tests, cognitive function, activities of daily living, or parkinsonism. CONCLUSION: Our results suggest that Yokukansan improves BPSD in both PD and PDD patients without worsening their cognitive function, ability to perform activities of daily living, or parkinsonism.

BOTTOM LINE: This type of a clinical trial is called a crossover study and is not the best evidence, but it is very promising and builds a plausible case for this type of natural therapy. Basically in a crossover trial, each participate gets both treatments being tested so they act like their own “control”.  In this case, the treatment vs no treatment.   They are hard to perform correctly so that the results are truly not due to chance alone.   However, in this case this small study shows something that was previously modeled in rats.  Specifically that this traditional Japanese medicine can improve daily living in patients living with this type of dementia.  It’s a step in the right direction.

Structural characterization of trace stilbene glycosides in Lysidice brevicalyx Wei using liquid chromatography/diode-array detection/electrospray ionization tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 20;

Authors: Hu Y, Qu J, Liu Y, Yu S, Li J, Zhang J, Du D

The mass fragmentation patterns of stilbene glycosides isolated from the genus Lysidice were investigated by negative ion electrospray ionization tandem mass spectrometry, and the influence of collision energy on their fragmentation behavior is discussed. It is found that the presence of the Y(0)(-) and B(0)(-) ions in the MS(2) spectra is characteristic for 1–>6 linked diglycosyl stilbenes, while the Y(0)(-), Y(1)(-), and Z(1)(-) ions are representative ions of 1–>2 linked diglycosyl stilbenes. These results indicate that ESI-MS(n) in the negative ion mode can be used to differentiate 1–>6 and 1–>2 linked diglycosyl stilbenes. Based on the fragmentation rules, 9 new trace constituents were identified or tentatively characterized in a fraction of Lysidice brevicalyx by using HPLC/HRMS and HPLC-DAD/ESI-MS(n). The results of the present study can assist in on-line structural identification of analogous constituents and targeted isolation of novel compounds from crude plant extracts.

BOTTOM LINE: In this case an endangered  plant whose bark has known antioxidant activity was evaluated. It turns out that some constituents of it show antioxidant activity at concentrations of 10⁻⁴ and 10⁻⁵ mol/L.  What does this mean??  It means ULTRA-TINY amounts of it show antioxidant activity, but are limited to SOME of the constituents or parts. The whole plant is not antioxidant.  This goes against some naturopathic holism principles, but otherwise we may find consuming 99% of something does no good (or even harm) and 1% leads to the effect we want.  This highly specific technology will allow us to figure that out. Then it will be up to us what extracts or parts we wish to consume rather than doing it blindly.

Nardostachys jatamansi Protects Against Cerulein-Induced Acute Pancreatitis.

Pancreas. 2009 Nov 23;

Authors: Bae GS, Park HJ, Kim DY, Song JM, Kim TH, Oh HJ, Yun KJ, Park RK, Lee JH, Shin BC, Sim HJ, Hong SP, Song HJ, Park SJ

OBJECTIVES:: Nardostachys jatamansi belonging to the family Valerianaceae has been used as a remedy for stomach and skin ailments in Korea. The effect of N. jatamansi on acute pancreatitis (AP) has not been defined. Therefore, we investigated the effect of N. jatamansi on cerulein-induced AP. METHODS:: In the pretreatment group, N. jatamansi was administered orally to mice at 10 and 20 mg/kg for 5 days, and the mice were intraperitoneally injected with the stable cholecystokinin analogue cerulein hourly for 6 hours. In the posttreatment group, cerulein was injected hourly for 6 hours, and N. jatamansi was administered at the indicated time (1, 3, and 5 hours after the first cerulein injection) and dose (10 and 20 mg/kg) during the cerulein injection. Blood samples were taken 6 hours later to determine the serum amylase, the lipase, and the cytokine levels. The pancreas and the lung were rapidly removed for morphologic examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. RESULTS:: Nardostachys jatamansi treatment attenuated the AP, as shown by the histological examination results of the pancreas and the lung, reductions in pancreatic edema, neutrophil infiltration, serum amylase and lipase levels, serum cytokine levels, and messenger RNA expressions of inflammatory mediators. CONCLUSIONS:: These results suggest that N. jatamansi attenuates the severity of AP and pancreatitis-associated lung injury.

BOTTOM LINE: In order to test what works in the animal basic science laboratory model, various diseases and conditions are induced or caused by substances.  In this case the substance cerulein induced acute pancreatitis in the animal model so that nardostachys jatamansi could be tested as a remedy. Nardostachys jatamansi is otherwise known as a Himlayan plant by the name of Spikenard. As you can see in the results, via modulation of very complex biochemical processes Spikenard may be useful to test against acute pancreatitis in humans.  

Effect of Nourishing “Yin”-Removing “Fire” Chinese herbal mixture on hypothalamic kisspeptin expression in female precocious rats.

J Ethnopharmacol. 2009 Nov 17;

Authors: Sun Y, Perry GN, Yu J, Chen B, Tian Z

AIM: The present study aims to investigate the effect of Nourishing “Yin”-Removing “Fire” herbal mixture, a Chinese herb-based formulation, on hypothalamic kisspeptin expression in danazol-induced female precocious model rats. MATERIALS AND METHODS: The female Sprague-Dawley rats were divided into intact normal (N), central precocious puberty (CPP) model (M), vehicle without CPP (V), CPP model exposed to herbal mixture (HM) and CPP model exposed to saline (S) groups. At postnatal day 5, a single subcutaneous injection of 300mug of danazol was administered to induce CPP model rats. From P15, rats in the HM group were continuously gavaged with the 1ml/50g body weight mixture, until 2 consecutive regular estrous cycles were established. The hypothalamic Kiss-1 expression was detected by RT-PCR and immunohistochemistry. RESULTS: The day of vaginal opening and establishment of two regular estrous cycles were delayed in the HM group compared with M and S groups (P<0.05, respectively). The level of hypothalamic Kiss-1 mRNA and the number of kisspeptin-immunoreactive (kisspeptin-ir) cells in the arcuate nucleus (ARC), preoptic area (POA) and periventricular nucleus (PeN), were decreased significantly in the HM group compared with the M and S groups (P<0.01, respectively) on the day of onset-puberty. These results indicate that the kisspeptin signaling pathway might be involved in the effect of herbal mixture treatment on CPP.

BOTTOM LINE: This is yet another example of highly refined bio-pathway therapy research going on in the complementary and alternative ethnopharmacology world.   Taking an herb and seeing a result is not a simple process folks.  It does not just go A ==> B.  You need a PhD to understand the details here, so don’t worry if it seems like gibberish to you.   The point is that the kisspeptin/KISS1R system has a crucial role in the initiation of sexual maturation across mammalian species and maintenance of the normal reproductive function.  Chinese TCM components may help unlock the problems surrounding “precocious” or early puberty.  In addition, understanding kisspeptin and KISS1R physiology may aid the development of new reproductive therapies, both promoting fertility and contraception.

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin.

Evid Based Complement Alternat Med. 2009 Nov 20;

Authors: Lu TC, Liao JC, Huang TH, Lin YC, Liu CY, Chiu YJ, Peng WH

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by lambda-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-alpha activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine.

BOTTOM LINE: Pogostemon cablin is other wise known as patchouli (patchouly or pachouli) oil, an essential oil.  Yes, the same one that has been used as a heavy perfume.  It has been used as a snakebite venom antidote,  aromatherapy relaxation,  and treatment of headaches, colds, nausea, diarrhea, and abdominal pain.  While this does not prove that it works to treat  all of these problems, it lends some scientific research credibility and plausibility towards such anti-inflammatory and pain relief uses.