http://bloomideas.blogspot.com/2006/09/exc...sons-stash.html
`When Willie Nelson’s bus was searched on Monday in Breaux Bridge, LA on Interstate 10, a “routine traffic stop” turned into a drug bust. Louisiana state troopers found more than a pound and a half of marijuana (0.7 kg) and more than three ounces (91 grams) of psilocibin mushrooms. See photo above’
http://www.hindu.com/thehindu/holnus/008200610080355.htm
`Some participants still have not had a drink 40 years after the trials. For the past five years, Dr. Erika Dyck has been unearthing some intriguing facts related to a group of pioneering psychiatrists who worked in Saskatchewan, Canada in the ’50s and ’60s.
Among other things, the University of Alberta history of medicine professor has found records of the psychiatrists’ research that indicate a single dose of the hallucinogenic drug LSD, provided in a clinical, nurturing environment, can be an effective treatment for alcoholism.
Her findings are published this month in the journal Social History of Medicine.’
http://www.cnn.com/2006/WORLD/americas/10/...reut/index.html
`Canadian troops fighting Taliban militants in Afghanistan have stumbled across an unexpected and potent enemy — almost impenetrable forests of marijuana plants 10 feet tall.
General Rick Hillier, chief of the Canadian defense staff, said Thursday that Taliban fighters were using the forests as cover. In response, the crew of at least one armored car had camouflaged their vehicle with marijuana. [..]
Even successful incineration had its drawbacks.
“A couple of brown plants on the edges of some of those [forests] did catch on fire. But a section of soldiers that was downwind from that had some ill effects and decided that was probably not the right course of action,” Hiller said dryly.’
My Banisteriopsis caapi. Received as rooted cutting from planthelper in January 2005. The roots had grown far out from the bottom of the pot so I cut them back and it was just okay, no sign of stress.
Here is the plant as of now (October 2006):
And here's how it looked in February 2005:
This morning I checked my plant for the sign of underside small tubes or darts at the leaf vein axils, and found that almost all the leaves on my plant do not have this unique characteristic. Only about 3 leaves have developed such thing.
Here are the pics of four leaves I took. The first 3 leaves do have the "V-tube" characteristic, whereas the other leaves look just like the pict at the bottom right corner.
Hi all, been trying to figure out this blog stuff & put some photos up. I've come to the conclusion that I am slightly retarded but I will persist.
Guess which one is named cock & balls
Willing to trade cacti!! let me know what you have. ..
I'm looking for T. Bridgesii Monstrose at the moment. .. will trade for T pachanoi pedro/s or others!
There is no common English name for this leaf, though it is sometimes mistakenly referred to as "betel leaf" or "wild betel leaf". They are sold in bunches, still on the stems, at Asian shops where they are called by their Thai name, cha plu, or the Vietnamese name, bo la lot. Though of the same family (Piperaceae) as the betel leaf, karuk is a finer, tender leaf, brighter green and with distinct veins. It is more delicate in flavour than betel leaf though still slightly pungent, and is eaten raw in Thai cuisine, especially as a leafy wrapping for snacks and appetisers called miang.
Sixteen compounds were isolated from the fresh roots of Piper sarmentosum. Seven of these have been isolated from the fruits and leaves of this plant: the aromatic alkene (1), 1-allyl-2-methoxy-4,5-methylenedioxybenzene (4), beta-sitosterol, pyrrole amide (6), sarmentine (10), sarmentosine (13) and pellitorine (14). (+)-Sesamin (2), horsfieldin (3), two pyrrolidine amides 11 and 12, guineensine (15) and brachystamide B (16).
K. Heyne in his book 'De Nuttige Planten van Indonesie" describes the use of karuk leaves to cure asthma, i.e. by rubbing crushed leaves around the neck. The most important active compound in this respect is the pyrrole amide, which acts by promoting expectoration. Chinese Medicinal Herb of Taiwan also mentioned Piper sarmentosum as a medicinal plant with warming, anti-swelling and anaesthetic properties.
In Indonesia, a decoction of the boiled leaves has been known to be effective in treating malaria, asthma, coughs, flu, rheumatism, pleurisy and lumbago. The root is a remedy for toothache and may be made into a wash for fungoid dermatitis on the feet. The leaves are also reported to contain antioxidant property.
In Laos it is used in salad. In Malaysia (where they are called daun kadok) the leaves are shredded for ulam (a mixture of fresh herbs). In one of the top hotels in Kuala Lumpur, the chef used the leaves in a recipe which was not traditional: a cross-culture creation midway between a fish terrine and the local Nonya otak-otak, a highly spiced fish paste. It was formed in a triangular mould lined with daun kadok leaves, turned out on a serving dish, then cut in elegant triangular slices.
Otak-otak is usually pressed between coconut leaves or strips of banana leaves and grilled over coals, often at roadside stalls. The coconut or banana leaf wrapper is stripped away and discarded after the layer of fish is eaten. In the hotel presentation, the soft P. sarmentosum leaf, no thicker than spinach, was eaten with the fish.
Purchasing and storing: Choose bright green, uncrushed leaves which are not faded or limp. Leaves can be kept wrapped loosely in damp paper and refrigerated for a day or two. If leaves need reviving, try soaking for 2 or 3 hours in cold water to which a spoonful of sugar has been added. This also sweetens the flavour of the leaves.
Recipe: Leaf-Wrapped Snacks
1 bunch karuk leaves
Fillings
200 g/7 oz shredded cooked pork, or chicken, or small shelled prawns
90 g/3 oz/1/2 cup roasted, salted peanuts
60 g/2 oz/1/2 cup sliced shallots
sliced chillies
3 tablespoons sliced pickled radish (optional)
Sauce
1 tablespoon palm sugar
1 tablespoon lime juice
1 tablespoon tamarind purée
2 tablespoons fish sauce
2 tablespoons dried shrimp floss (optional)
1/2 teaspoon crushed garlic
Wash the leaves well and soak in cold, lightly sugared water for a couple of hours. Pat leaves dry. Prepare the fillings and arrange around a platter, with the leaves. Mix sauce ingredients in a small bowl. Each person puts their choice of fillings on a leaf, wraps it and dips the leaf in the sauce before eating.
Note: For special occasions, the leaf snacks may be presented already wrapped, and luxury ingredients such as crab meat included in the filling. The leaf parcel is secured with a cocktail stick.
Other Languages:
Indonesia: karuk, sirih tanah
Chinese : jia ju, xi ye qing wei teng, qing ju
Laos: phak i leut
Malaysia: daun kadok
Thailand: cha plu
Vietnam: bo la lot
References:
Chemical constituents of the roots of Piper sarmentosum
Chemical constituents and bioactivity of Piper sarmentosum
Natural antioxidants: Piper sarmentosum and Morinda elliptica
Neuromuscular blocking activity of methanolic extract of Piper sarmentosum leaves in the rat phrenic nerve-hemidiaphragm preparation
Adulticidal activity against Stegomyia aegypti (Diptera: Culicidae) of three Piper spp.
Hypoglycemic effect of the water extract of Piper sarmentosum in rats.
This Hawaiian baby woodrose (Argyreia nervosa) is a friendly gift from DC when I was in Melbourne in November 2005. Germinated easily from seeds, It's now climbing along a metal post next to my kratom tree, and growing upward, twining the kratom branches and twigs, creating a harmony. On the background you can see the kratom leaves. I was wondering why this plant is called "baby".
This Tabernanthe iboga is of the long pod variety. I received 11 seeds from Brian in April 2006. About 3 seeds germinated and currently I have two young plants. These are placed in small pots under the shade of a bush.
I have planted this miracle fruit in pot since 2001 and it's been growing so slowly. I started fruiting in about 3 years from seed. It loves acidic soil and will fruit under full sun or half.
I made an interesting experiment in the office where I work. I gave one fruit to one of my colleagues and asked them to eat it, then I prepared a sour mix of very thick lemon juice and a couple spoons of apple cider vinegar.
It was soooo amusing when I saw their face after they tasted the sour mix. They didn't understand how I did it and it took me quite some time to explain them about the plant while the other co-workers came and join the 'listener group'.
http://www.smh.com.au/news/national/sniffe...7827074300.html
`Drug sniffer dogs do little to identify drug dealers and often falsely identify people as carrying illegal drugs, a report by the Ombudsman said today.
It found only 19 people out of about 10,000 indicated by dogs as carrying drugs were successfully prosecuted for supplying drugs, despite the sniffer dogs program costing taxpayers hundreds of thousands of dollars.
The two-year investigation has questioned the need for laws which allow drug dogs to sniff people in public to detect drugs.’
GREETINGS ALL,
I'M NEW TO THIS SITE AND WOULD LIKE TO BEGIN BY OFFERING MY CONGRATS AND THANKS TO THE CREATORS. ALSO I'D LIKE TO ISSUE A CALL TO ALL SHAMANS IN SOUTHERN NSW/ACT AREA TO DROP ME A LINE AND SAY HI!!
MY PARTICULAR INTERESTS ARE NEUROPHYSIOLOGY/ DMT/ EVOLUTION/ AND THE EXPANSION OF THE COLLECTIVE CONSCIOUSNESS.
I'D REALLY ENJOY HEARING FROM ANYONE WITH SIMILAR INTERESTS IN MY AREA TO SHARE KNOWLEGDE/ THEORIES AND EXPERIENCES PAST, PRESENT AND FUTURE.
I AM (32YRS) AN UNDERGRADUATE MED SCIENCE STUDENT WITH SOME FIRST HAND PERUVIAN AYAHUASCA (DMT) EXPERIENCE. I AM A REGULAR TRAVELLER TO SOUTH AMERICA AND HAVE A CONSIDERABLE AMOUNT OF "IN COUNTRY" KNOWLEDGE/ CONTACTS.
I VERY HOPEFUL THAT THERE ARE OTHERS WHO WOULD ENJOY/ BENEFIT FROM THE INTERACTION.
YO
CHOW 4 NOW
MUCHOMUNDOS
http://pubs.acs.org/cgi-bin/sample.cgi/mpo.../mp060066m.html
A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology
`[..] Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of A aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
[..] Therefore, AChE inhibitors such as THC and its analogues may provide an improved therapeutic for Alzheimer’s disease, augmenting acetylcholine levels by preventing neurotransmitter degradation and reducing A aggregation, thereby simultaneously treating both the symptoms and progression of Alzheimer’s disease.’
http://www.breitbart.com/news/2006/08/09/0...2.rjv9k7v2.html
An American tourist who ran naked through a peaceful Swiss town, vandalized a church and escaped from police clutches by jumping into a lake could have been on hallucinogenic mushrooms, a local magistrate said.
The 34 year-old from Massachusetts, who has since been allowed to return home, ran amok in the western town of Morges, by Lake Geneva, two weeks ago,
He started babbling incoherently in the hotel lobby, stripped and ran naked along the quayside, broke a stained glass window in the nearby protestant temple with a stool and set a precious 1898 bible alight, police in Morges said.
After being seized and handcuffed by police, he made a leap for freedom into the lake and bit two people who tried to help him while he was hanging on to a boat.
Having recovered his senses, he later appeared before investigating magistrate Gilles Riva and "coherently" explained that he had eaten 'magic mushrooms' that he had bought in the Netherlands during a trip through Europe.
http://www.newscientist.com/article/dn9696...thin-hours.html
A drug used as a general anaesthetic may also work as a remarkably rapid antidepressant, according to a preliminary study.
The drug’s hallucinogenic side effects mean it is unlikely to be prescribed to patients, but it could pave the way to new faster-acting antidepressants, the researchers suggest.
Ketamine is used as an animal tranquiliser, but is perhaps better known as an illicit street drug, sometimes called “special K”. Now researchers have found the drug can relieve depression in some patients within just 2 hours – and continue to do so for a week.
One problem with current antidepressants is that they typically take weeks to kick in. Some studies have found that patients may face a high risk of suicide in the first week after starting an antidepressant treatment because of this lag time. So researchers have been searching for alternative drugs.
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http://www.breitbart.com/news/2006/07/25/0...1.hcv2gydp.html
`Police in France said they had thwarted an attempt by a group of marijuana smokers to roll the world’s longest joint by seizing a work-in-progress measuring 80 centimetres (32 inches) in length.
“At some point, these young people had wanted to craft a joint of 1.12 metres to beat the world record in the discipline and get it officially registered,” said a police officer in eastern France. [..]
During an investigation targeting a group of four smokers in the eastern Vosges area of France, police discovered the giant joint containing 70 grams of marijuana resin. It had not been finished because of a lack of tobacco.’
A human test of high purity Honokiol (approx 80 - 90% Honokiol content) consumed via capsule ---- personally conducted by the creator of this site --- suggests that for a person of average weight (160 lbs), a dose of 3-4 grams is well-tolerated. At a dose as high as 8 grams, the side effect is limited to nausea ... which is frequently the case with cancer drugs.
....
The administrator of this site (160 lbs), who does not have cancer, has already established that 3-4 grams of high purity Honokiol (80-90%) taken orally once weekly is non-toxic, and that 8 grams caused nausea at worst.
......
It would seem logical, based on the lab test-results with mice, that if a solution of Honokiol were to be injected directly into cancer-infected tissue in a human being via a long needle, it might kill large areas of cancer cells locally. This approach would be similar to that taken with direct injection into tissue of rabies victims, though with a cancer patient several different areas may require this approach at the same time. Whether this would ultimately slow metastasis is unknown, at it has never been tried.
....
2004 also saw the release of a study from the Institute of Medical Sciences at Tzi Chi University demonstrating that Honokiol acted as an anti-seizure agent in lab animal tests, by acting as a "selective blocker of the NMDA receptor" in the brain.
....
I have been fascinated by honokiol for a while now and want to create a record of research and comments about it for my own benefit as much as that of others interested in this field.
http://www.clltopics.org/Phyto/honokiol.htm
Honokiol
May 15, 2005
by Chaya Venkat
Sitting under a Magnolia Tree, Mint Julep in Hand
“Honokiol” Background
In our last Topics Alert I promised you a quick read on honokiol, a plant lignan isolated from the bark and/or seed cones of the Magnolia tree. The Chinese call it “hou po”, and use it to treat digestive disorders. The Japanese refer to it as “saiboku-to”, and sure enough they drink it as a tea to treat anxiety. It has been around as part of traditional medicinal practices for about 2,000 years, but it burst on the CLL scene just a few days ago when the research group from Dana Farber/Harvard Medical School published a cell line study in the latest issue of “Blood”. Their results are very interesting, but please remember these are cell line studies, CLL cells in glass dishes sitting on a lab bench. There are many steps and hurdles from there to mouse studies and finally human studies. If enough of us are really interested, maybe we can do a little something to speed up the process.
Honokiol and its sister compound Magnolol (see the structures below) received general media attention once before, in 2003, when Dr. Jack Arbiser and other researchers at Emory University evaluated a variety of natural product extracts, including magnolia seed cone extracts, looking for anti-angiogenesis compounds with potential as anti-tumor compounds. As you probably know by now, cancers grow by developing their own dedicated networks of blood vessels, so that oxygen and nutrients are stolen from healthy tissues to feed the malignant cells. Cutting off the blood supply to these tumors is a tried-and-true method for stopping their growth, a concept pioneered by Dr. Judah Folkman (my hero!). Compounds that can selectively retard the growth of blood vessels feeding the cancer would be promising candidates as anti-cancer drugs.
Arbiser’s group found that the active ingredients in the magnolia extracts were two biphenyl compounds, “honokiol” and “magnolol”, and these were potent anti-angiogenesis compounds. Not much surprise here - their findings agreed with a decade’s worth of western research and a couple of thousand years of traditional medicinal practice. Dr. Arbiser, et. al. found that honokiol was the more active of the two compounds . The good news is that there is no danger that all the magnolia trees in the world are going to be cut down in order to supply world demand for these compounds. These are small molecules, easily synthesized. Heck, I expect any half-way decent organic chemist can come up with methods of synthesis without breaking a sweat. How I wish I am not “retired” - I really do miss not having access to a well-quipped lab.
There is one little feature of Honokiol that is particularly useful: it can be taken orally and then it becomes systemically available throughout the body. Unlike other natural products such as EGCG from green tea, genistein from soybeans, curcumin from turmeric and resveratrol from red wine, all of which get destroyed to a great extent in the gut and liver (“first pass metabolic losses”), honokiol is capable of dispersing throughout the body. Tests using cute little lab mice showed that honokiol remains in the body long enough to be effective as a drug. It is not quickly broken down by the liver or excreted. Both honokiol and magnolol are small molecules, and they are able to penetrate lipid membranes of cells, likely to penetrate all the nooks and crannies. Dare we hope these compounds may be able to reach lymph nodes and bone marrow, locations that are much harder to reach with "fat lady" monoclonal antibody drugs such as Rituxan and Campath? I saved the best for last, the mechanism of action of honokiol does not seem to depend entirely on proper function of the p53 gene. In other words, even patients in “Bucket C” cytogenetics, those with the dreaded 17p (p53 gene) defects detected by FISH, even these hard cases may respond to this drug. That is welcome news, since so many drugs are ruled out for CLL patients with 17p deletions.
Honokiol: Harvard Highlights
This is the paper that started the ball rolling for me. It is the first abstract below in the Literature References section. Let us know if you want to read the full text article, we will help you locate it. I have made a bullet point list of some of the highlights of this important paper. Incidentally, the same issue of Blood also carried an article looking at the role of honokiol in multiple myeloma, another blood cancer.
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CLL cells from 19 untreated patients with B-CLL were incubated with various concentrations of honokiol for 6-24 hours; Each patients’ cells were sensitive to the cytotoxic effects of honokiol.
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There were no apparent correlations between sensitivity to honokiol and clinical characteristics, early and late Rai stage patients showed similar responses.
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CLL cells are more susceptible to honokiol-induced cell death compared to normal B-cells. This is important, there is not much point in killing cancer cells if in the process we kill the patient too. (See figure below, excerpted from the Harvard paper).
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Exposure of B-CLL cells to honokiol had no effect on bcl-2 levels, but the expression of bax, a protein that can promote apoptosis (programmed cell suicide), increases following honokiol treatment.
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Interleukin-4 (IL-4) is a cytokine known to be important in promoting the survival of B-CLL cells. For example, IL-4 makes CLL cells less susceptible to killing by fludarabine. Yet the pro-survival effects of IL-4 failed to protect the CLL cells from the killing effects of honokiol.
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Low-dose honokiol significantly increased the cytotoxicity of fludarabine, cladribine, and chlorambucil. This is good news, if it translates into lower doses of these powerful chemotherapy agents needed to get the same therapeutic result. The well documented toxicity of many chemotherapy agents is dose dependent, getting the same bang for less buck would be a very good thing.
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Pharmacokinetic studies in mice revealed that honokiol is readily absorbed and maintained in the plasma for over 10 hours. Administration of up to 120 mg/kg body weight for 30 days was well tolerated.
Dosage: How Much Is Enough? How Much Is Too Much?
I looked pretty hard for red flags on the toxicity issue, and I have not found any, thus far. There was brouhaha a while ago about a Belgian weight loss drug that caused some liver and kidney problems, and initially the culprit was thought to be honokiol. Closer scrutiny seemed to suggest that there were other ingredients in the weight loss concoction that may have been responsible, not honokiol. Nevertheless, the suspicion lingers that honokiol may cause liver / kidney toxicity. “Supplement Watch”, a reasonably well informed Internet site that looks at toxicity issues of many herbal compounds, gives honokiol pretty good grades, you can read their review by clicking on the link below.
http://www.supplementwatch.com/supatoz/sup...upplementId=380
You may also have heard of magnolia bark extracts as the active ingredients in several diet and weight loss products on the market. “Cortislim” and “Relacore” claim to help weight loss by reducing the amount of cortisol in your body. Cortisol is a stress hormone and it increases as we grow older, and their theory (substantially unproven) is that their products reduce cortisol levels and this helps weight loss. But you should also be aware there are class action lawsuit against the makers of Cortislim / Relacore. Don’t you just love our litigious society? Hard to avoid lawsuits when there is advertising hype coupled with gullible consumers looking for an easy fix. Read all about the lawsuits by clicking on the links below:
http://stress.about.com/od/cortisol/a/cortislim.htm
https://www.lawyersandsettlements.com/case/relacore
But sufficient credible research now exists demonstrating honokiol is a potent and powerful drug, at the right dosage. Oral bioavailability (fancy talk for saying it is possible to take it as a pill) combined with very little toxicity makes for an intriguing drug candidate. However, just because it comes from a “natural” source does not guarantee it is safe at all dosages and over a long period of time. The fact that Chinese and Japanese people have been brewing tea from magnolia bark and drinking it for a long time is not quite enough either. Let’s see: I understood that the traditional use involved making a decoction of the bark with hot water, any where from 4-8 grams of the bark, containing 1-2% of the active ingredient. Brewing tea is far from 100% efficient in getting at the active compounds, and in fact heat may destroy some of the active ingredients. Let us assume, optimistically, that the brewed decoction is successful in getting a quarter of the active ingredients present, efficient to the tune of 25%. Typically, there is more magnolol than honokiol in the bark, but let us assume for now that the two are present in equal amounts. Here is how the dosage works, under these assumptions:
(8 grams bark) X (1% honokiol + 1% magnolol) X (25% brewing efficiency) = 0.02 grams honokiol, 0.02 grams magnolol
That means a person drinking tea made from 8 grams of magnolia bark may get two hundredths of a gram of honokiol, using our optimistic assumptions. By the way, I am told the magnolia bark tea tastes really foul, bitter as they come. I suggest you stick to drinking green tea.
There are several products on the herbal medicine websites that claim to contain honokiol. First, you have to cross the bridge of accepting the manufacturer’s claims of the composition of their product, no small assumption. There is almost no formal verification of the claims that these companies can make, it is entirely up to the consumer to vote with his wallet. Assuming the composition is as claimed, we are still looking at a maximum of 1-2% active ingredients, and at the generally recommended dose of 250 milligram capsule, 3 times daily, it still works out to a hundredth of a gram of honokiol per day. Not cheap at the price charged for some of these miracle cures.
Doses at a hundredth of a gram of honokiol per day may be good enough for settling nerves and relieving stress and anxiety (there is more credible evidence on this front - a "natural" version of Valium - compared to the weight loss claims), but dosages at this low level may not be enough for treating cancer. Scroll back up and look at the diagram from the Harvard paper. Nothing much happens in terms of cell kill, until a certain threshold is crossed. At the higher doses of honokiol needed to kill CLL cells, and possibly daily dosing over long periods of time, new and unexpected toxicities may show up. Some of the mice studies I saw used doses ranging from 0.01 grams / kilogram body weight up to 0.25 grams / kilogram. Most of us are quite a bit heavier than mice. Assuming a body weight of 70 kilograms, we are looking at doses ranging from 0.7 grams and up. That is a lot more honokiol than you can get by drinking magnolia bark tea. The million dollar question is the usual one, the balance of risks versus rewards. We are all pretty grown up here; we understand that a certain amount of toxicity is unavoidable in any cancer therapy, just so long as the rewards justify the risks. At this point in time, we do not have enough information to judge either the risks or the rewards of ingesting these high levels of honokiol.
What Should We Do Next?
I went through the above calculations to show you that the levels used in traditional medicine or by popular “miracle” potions out there do not begin to approach the dosages needed for robust efficacy as cancer therapy. That is why we need well-designed clinical trials conducted by reputable researchers with no axe to grind, dose escalation studies to determine safety limits and so on. Individual testimonials do not cut it for me, for this or any other drug. There is too much variability in patients and all too often subjective evaluation and wishful thinking cloud the issues. I know several CLL patients who literally go “postal” when their cherished “alternative medicines” are questioned. Anyone remember the fuss about coral calcium? I believe the pusher of that particular miracle is under criminal indictment. The latest Blood article from Harvard as well as other cancer studies listed below are encouraging and intriguing leads from very reputable scientists, and I would be kidding if I said I was not interested or impressed. I would be particularly interested in honokiol as a low toxicity route to slowing down the rate at which the CLL grows, and increasing the length of remission periods after more conventional therapy to get rid of the bulk of the disease. But each and every one of the abstracts below talks of cell line studies, or at best mice studies. That is a long way from general use in human CLL patients. This latest paper in Blood is a good start, since this is the first time that honokiol was specifically looked at in terms of CLL. I am willing to get in touch with the Harvard researchers, see if there is anything we can do speed things up, but I need to hear from you.
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Are you interested in seeing priority given to honokiol research?
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Would you support honokiol clinical trials with your money?
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With you consider participating in honokiol clinical trials when / if they were to become available?
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Would you allow us to use your name and /or email response to help convince the researchers the patient community is solidly behind this effort?
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Do you have suggestions how CLL Topics can support and speed up this effort?
Remember, the clout CLL Topics has with the research community is only as good as our grassroots support and solidarity of our membership. Last count, our website gets more than 24,000 visits each month. I doubt any of you visit us to see the pretty pictures PC has on the website, or because you relish my dubious sense of humor. Since you have reason to visit our site, it makes sense to speak up and make your voice heard.
Abstracts:
Blood. 2005 Mar 31; [Epub ahead of print]
The natural product Honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells.
Battle TE, Arbiser J, Frank DA.
Department of Medical Oncology, Dana-Faber Cancer Institute, Boston, MA; Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
B-CLL remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Honokiol is a natural product known to possess potent anti-neoplastic and anti-angiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspases 3, 8, and 9 and cleavage of PARP. Exposure of B-CLL cells to honokiol resulted in up-regulation of bax and down-regulation of the expression of the key survival protein Mcl-1, which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pre-treated with IL-4, a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the pro-survival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents.
PMID: 15802533
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World J Gastroenterol. 2004 Dec 1;10(23):3459-63.
Honokiol: a potent chemotherapy candidate for human colorectal carcinoma.
Chen F, Wang T, Wu YF, Gu Y, Xu XL, Zheng S, Hu X.
Cancer Institute, Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang province, China.
AIM: To investigate the anticancer activity of honokiol on RKO, a human colorectal carcinoma cell line in vitro and in vivo, and to evaluate its possible use in clinic.
METHODS: In vitro anticancer activity of honokiol was demonstrated by its induction of apoptosis in tumor cells. We analyzed cell proliferation with MTT assay, cell cycle with flow cytosmeter, DNA fragment with electrophoresis on agarose gels. To test the mechanism of honokiol-induced apoptosis, Western blotting was used to investigate the factors involved in this process. The pharmacokinetics study of honokiol was tested by high phase liquid chromatography. In in vivo study, Balb/c nude mice were incubated with RKO cells. Honokiol was injected intraperitoneally every other day into tumor bearing Balb/c nude mice.
RESULTS: Our results showed that honokiol induced apoptosis of RKO cells in a time- and dose-dependent manner. At 5-10 microg/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades. Pharmacokinetics study demonstrated that, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h. In nude mice bearing RKO-incubated tumor, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice.
CONCLUSION: With its few toxicity to normal cells and potent anticancer activity in vitro and in vivo, honokiol might be a potential chemotherapy candidate in treating human colorectal carcinoma.
PMID: 15526365
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World J Gastroenterol. 2004 Aug 1;10(15):2205-8.
Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO.
Wang T, Chen F, Chen Z, Wu YF, Xu XL, Zheng S, Hu X.
Cancer Institute, Second Hospital of Medicine, College of Zhejiang University, Hangzhou 310009, Zhejiang Province, China.
AIM: To investigate the signal pathway of honokiol-induced apoptosis on human colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes were involved in honokiol-treated RKO cells.
METHODS: Cell cycle distribution and subdiploid peak were analyzed with a flow cytometer and DNA fragment with electrophoresis on agarose gels. Transcriptional level of Bax, Bcl-2, Bid and Bcl-xl was accessed by RT-PCR. Western blotting was used to measure p53 protein expression and other factors related to apoptosis. Proliferation inhibition of two cell lines (RKO, SW480) with high expression of p53 and one cell line with p53 negative expression (LS180) was monitored by MTT assay.
RESULTS: Honokiol induced RKO cell apoptosis in a dose-dependent manner. The mRNA expression level and protein level of Bid were up-regulated while that of Bcl-xl was down-regulated, but no changes in Bax and Bcl-2 were observed. Western blotting showed p53 expression had no remarkable changes in honokiol-induced RKO cell apoptosis. LS180 cells treated with honokiol exhibited apparent growth inhibition like RKO cells and Sw480 cells.
CONCLUSION: Honokiol can induce RKO cells apoptosis through activating caspase cascade by p53-indepenent pathway.
PMID: 15259066
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Int J Mol Med. 1998 Dec;2(6):671-3.
Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells.
Hibasami H, Achiwa Y, Katsuzaki H, Imai K, Yoshioka K, Nakanishi K, Ishii Y, Hasegawa M, Komiya T.
Faculty of Medicine, Mie University, Japan.
The exposure of human lymphoid leukemia Molt 4B cells to honokiol led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with honokiol. The fragmentation by honokiol of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition by honokiol of Molt 4B cells results from the induction of apoptosis in the cells.
PMID: 9850734
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J Biol Chem. 2003 Sep 12;278(37):35501-7. Epub 2003 Jun 19.
Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo.
Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell PM, Govindarajan B, Der CJ, Battle T, Frank DA, Ye K, Murad E, Dubiel W, Soff G, Arbiser JL.
Department of Dermatology, Emory University School of Medicine, Atlanta, GA.
Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent.
PMID: 12816951
