Gibbledygook's anti-viral log

[gibbledygook]

1: Chem Pharm Bull (Tokyo). 1992 Feb;40(2):531-3.Links
Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumor-promoting activities.Konoshima T, Kokumai M, Kozuka M, Iinuma M, Mizuno M, Tanaka T, Tokuda H, Nishino H, Iwashima A.
Kyoto Pharmaceutical University, Japan.

To search for possible anti-tumor-promoters, fourteen flavones obtained from the root of Scutellaria baicalensis were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Among these flavones, 5,7,2'-trihydroxy- and 5,7,2',3'-tetrahydroxyflavone showed remarkable inhibitory effects on the EBV-EA activation, and the effect of the latter on Raji cell cycle was also examined by flow cytometer. These two flavones exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

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[gibbledygook]

Another reason to take capsaicin:

1: J Pharmacol Exp Ther. 2001 Oct;299(1):238-46. Links
Capsaicin inhibits Jurkat T-cell activation by blocking calcium entry current I(CRAC).Fischer BS, Qin D, Kim K, McDonald TV.
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Capacitative calcium entry (CCE) through stores-operated Ca2+ channels is an absolute requirement for normal activation of T lymphocytes. Organic blockers/inhibitors of the channel(s) that carry the inward Ca2+ current (I(CRAC)) responsible for CCE are few. Here we show that capsaicin, the pungent ingredient of hot chili pepper, blocks receptor-stimulated Ca2+ entry in Jurkat T cells. Indo-1 measurements of intracellular calcium show that capsaicin blocks CCE without affecting release of inositol-1,4,5-trisphosphate-sensitive internal Ca2+ stores with an IC50 of 32 microM. Block of Ca2+ entry by capsaicin is identical whether CCE is evoked by T-cell receptor (TCR) stimulation, heterologous muscarinic M1 receptor stimulation, or via thapsigargin depletion of internal Ca2+ stores. Patch-clamp experiments show that capsaicin rapidly and reversibly blocks I(CRAC) with an identical dose response as seen with indo-1 measurements. The major voltage-gated K+ channel in Jurkat cells, Kv1.3, is also blocked by capsaicin. Although Kv1.3 block may contribute to reducing CCE by changes in membrane potential, block of I(CRAC) is the primary mechanism by which capsaicin reduces CCE. Capsaicin analogs capsazepine and resiniferatoxin also produce inhibition of CCE via block of I(CRAC). Upon application of capsaicin to Jurkat cells in culture we observed an inhibition of interleukin-2 (IL-2) production in response to TCR stimulation. The dose dependence of capsaicin's reduction of IL-2 was comparable with its block of I(CRAC), thereby illustrating the functional relevance of capsaicin's block of lymphocyte CCE. Thus, capsaicin and its numerous analogs may have potential use as immunomodulatory drugs and should be further investigated in models of inflammation and T-cell activation.

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1: Curr Med Chem. 2006;13(19):2241-51. Links
Regulation of inflammatory responses by sensory neurons: molecular mechanism(s) and possible therapeutic applications.Okajima K, Harada N.
Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences, Japan. whynot@med.nagoya-cu.ac.jp

Capsaicin-sensitive sensory neurons are nociceptive neurons that release calcitonin gene-related peptide (CGRP) on activation. Since CGRP has potent vasodilatory activity, it has long been considered to be involved in aggravation of inflammation such as tissue hyperemia and edema. However, since ablation of the sensory fibers can result in a marked increase in the severity of inflammation and reperfusion-induced tissue inflammatory responses are enhanced in congenital CGRP-knockout mice, the sensory neurons have been shown to play a role in the maintenance of tissue integrity by regulating local inflammatory responses. We demonstrated in rodents that stimulation of sensory neurons reduces hypertension, stress-induced gastric mucosal injury, reperfusion-induced liver injury, and endotoxin-induced shock responses by attenuating inflammatory responses such as increases in both tissue levels of tumor necrosis factor (TNF) and tissue accumulation of neutrophils. Attenuation of inflammatory responses by sensory neuron activation can be explained mainly by CGRP-induced increase in the endothelial production of prostacyclin (PGI(2)). Since inflammatory responses are critically involved in the development of a wide variety of diseases, pharmacological stimulation of sensory neurons might contribute to treatment of various pathologic conditions. In this review, the authors describe molecular mechanism(s) by which sensory neuron activation inhibits TNF production, thereby attenuating inflammatory responses. Furthermore, the authors discuss some clinically useful therapeutic agents that are capable of activating sensory neurons and raise the possibility that pharmacological stimulation of sensory neurons is the new paradigm for future therapeutic strategies.

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1: J Pharmacol Exp Ther. 2007 Aug;322(2):582-90. Epub 2007 May 23. Links
Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation.Nakayama T, Harada N, Asano M, Nomura N, Saito T, Mishima A, Okajima K.
Departments of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Japan.

We recently demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons reduces spinal cord injury (SCI) by inhibiting neutrophil activation through an increase in the endothelial production of prostacyclin (PGI(2)). Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP), reduces ischemia/reperfusion (I/R)-induced tissue injury. However, its precise therapeutic mechanism(s) remains to be elucidated. In the present study, we examined whether ANP reduces I/R-induced spinal cord injury by enhancing sensory neuron activation using rats. ANP increased CGRP release and cellular cAMP levels in dorsal root ganglion neurons isolated from rats in vitro. The increase in CGRP release induced by ANP was reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation, or with (9S, 10S, 12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy- 1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzodiazocine-10-carboxylic acid hexyl ester (KT5720), an inhibitor of protein kinase A (PKA), suggesting that ANP might increase CGRP release from sensory neurons by activating PKA through an increase in the cellular cAMP level. Spinal cord ischemia was induced in rats using a balloon catheter placed in the aorta. ANP reduced mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. ANP significantly enhanced I/R-induced increases in spinal cord tissue levels of CGRP and 6-keto-prostaglandin F(1alpha). a stable metabolite of PGI(2). ANP inhibited I/R-induced increases in spinal cord tissue levels of tumor necrosis factor and myeloperoxidase. Pretreatment with 4'-chloro-3-methoxycinnamanilide (SB366791), a specific vanilloid receptor-1 antagonist, and indomethacin reversed the effects of ANP. These results strongly suggest that ANP might reduce I/R-induced SCI in rats by inhibiting neutrophil activation through enhancement of sensory neuron activation.

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1: J Immunol. 2007 Mar 1;178(5):3260-4. Links
Immunotherapy of tumors with neuroimmune ligand capsaicin.Beltran J, Ghosh AK, Basu S.
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1601, USA.

Red chili pepper (Capsicum frutescens) is a highly consumed spice throughout the world. Its principal pungent ingredient is the phenol capsaicin (8-methyl-N-vanillyl-6-nonenamide). Capsaicin causes neurogenic inflammation and has analgesic and anti-inflammatory activities. We have observed previously that dendritic cells, a key cell type in immune responses, have the receptor for capsaicin, and engagement of this receptor has powerful immune consequences. In this study, we demonstrate that intratumoral administration of capsaicin into a preexisting tumor results in retarded progression of the injected tumor regardless of whether the tumor is at its early or late stage. Furthermore, it leads to significant inhibition of growth of other, uninjected tumors in the same animal. Capsaicin-elicited immunity is shown to be T cell-mediated and tumor-specific. These results reflect the immunological potency of a neurological ligand in modulating immune response against an established tumor

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BUT

1: Brain Res. 2005 Sep 21;1056(2):139-44. Links
Involvement of caspase cascade in capsaicin-induced apoptosis of dorsal root ganglion neurons.Jin HW, Ichikawa H, Fujita M, Yamaai T, Mukae K, Nomura K, Sugimoto T.
Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.

Capsaicin induces apoptosis in some types of neurons, but the exact molecular mechanism remains unclear. In this study, capsaicin was systemically administrated in newborn rats and the dorsal root ganglion (DRG) neurons were examined for caspase-immunoreactivity. Capsaicin-induced neuronal apoptosis was revealed by TUNEL. TUNEL-positive neurons rapidly increased, reaching the peak at 24 h post-injection when 10.6% of DRG neurons were apoptotic. Neurons expressing immunoreactivity for activated caspases-9 and -3 concomitantly increased. At 24 h, 15.9% and 17.7% of DRG neurons exhibited immunoreactivity for caspase-9 and caspase-3, respectively. DNA fragmentation signal and caspase-immunoreactivity were detected in less than 0.5% of DRG neurons of vehicle control rats. The immunoreactivity and TUNEL-positivity returned to the vehicle control level by 120 h. Double label immunohistochemistry revealed co-expression of caspase-9 and DNA fragmentation or caspase-3 and DNA fragmentation. These results suggest that the caspase cascade is involved in the primary neuronal apoptosis induced by neurotoxin capsaicin.

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[gibbledygook]

Today I started the new tea which consists of the following:
20g rehmannia radix preparata
20g rehmannia radix
20g eucommiae cortex
20g gentianae macrophyllae radix
10g glycyrrhizae radix
20 ligustri lucidi fructus
15g paeoniae radix rubra
15g liquidambaris fructus
15g curcumae longae rhizoma
30g ganoderma
20g angelica sinensis radix
15g jujubae fructus

I think I may have found the final herb for my ongoing additional herbal treatment which now consists of 7.2g of the bioavailable life extension curcumin, 30mg of bioperine, 2.4g of capsaicin, circa 6g of skullcap and circa 5.5g of astragalus. I shall order some salviae miltiorrhiza for its anti-coagulant properties.

1: Ann Pharmacother. 2001 Apr;35(4):501-4. Links
Interaction between warfarin and danshen (Salvia miltiorrhiza).Chan TY.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories. tykchan@cuhk.edu.hk

OBJECTIVE: To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review. STUDY SELECTION AND DATA EXTRACTION: All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed. DATA SYNTHESIS: Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III-like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.

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I want an antithrombin III herb because:

1: Nature. 2008 Feb 28;451(7182):1076-81. Epub 2008 Feb 17. Links
Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets.Han MH, Hwang SI, Roy DB, Lundgren DH, Price JV, Ousman SS, Fernald GH, Gerlitz B, Robinson WH, Baranzini SE, Grinnell BW, Raine CS, Sobel RA, Han DK, Steinman L.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.

Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque. Comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells. Administration of mutant forms of recombinant activated protein C showed that both its anticoagulant and its signalling functions were essential for optimal amelioration of experimental autoimmune encephalomyelitis. A proteomic approach illuminated potential therapeutic targets selective for specific pathological stages of MS and implicated participation of the coagulation cascade.

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Hirudin on wikipedia today:

Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches (such as Hirudo medicinalis) that has a blood anticoagulant property. This is fundamental for the leeches’ alimentary habit of hematophagy, since it keeps the blood flowing after the initial phlebotomy performed by the worm on the host’s skin.

In 1884, the British physiologist John Berry Haycraft discovered that the leech secreted a powerful anticoagulant, which he named hirudin, though it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length, hirudin is made up of 65 amino acids. These amino acids are organised into a compact N-terminal domain containing three disulfide bonds and a C-terminal domain which is completely disordered, when the protein is un-complexed in solution.[1][2] Natural hirudin contains a mixture of various isoforms of the protein. However, recombinant techniques can be used to produce homogeneous preparations of hirudin.[3]


[edit] Biological activity
A key event in the final stages of blood coagulation is the conversion of fibrinogen into fibrin by the serine protease enzyme thrombin.[4] Thrombin is produced from prothrombin, by the action of an enzyme, prothrombinase, in the final states of coagulation. Fibrin is then cross linked by factor XIII to form a blood clot. The principal inhibitor of thrombin in normal blood circulation is antithrombin III.[3] Similar to antithrombin III, the anticoagulatant activity of hirudin is based on its ability to inhibit the pro-coagulant activity of thrombin.

Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin III hirudin binds to and inhibits only the activity of thrombin forms with a specific activity on fibrinogen.[3] Therefore, hirudin prevents or dissolves the formation of clots and thrombi (i.e. it has a thrombolytic activity), and has therapeutic value in blood coagulation disorders, in the treatment of skin hematomas and of superficial varicose veins, either as an injectable or a topical application cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such as heparin, as it does not interfere with the biological activity of other serum proteins and can also act on complexed thrombin.

It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein using recombinant biotechnology has been developed. This has led to the development and marketing of a number of hirudin based anticoagulant pharmaceutical products such as lepirudin (Refludan) and Desirudin (Revasc/Iprivask). Several other direct thrombin inhibitors are derived chemically from hirudin.

[SarahLonglands]

I hope, Alex, that you aren't someone like me who bleeds profusely at the slightest knock or scratch, because anything anticoagulant might not be a good idea.

Just a friendly warning.

Sarah

[CureOrBust]

I have been reading your thread, with interest in capsaicin. I tried to get it at a local health store, but they were out. The label on the shelf said the "strength" of the formulation was 40000 BTU's (or some unit to do with heat, which makes sense). Do you have a rating of "strength" for your capsules?

I also see you had issues with taking high doses, do you take it as a single big dose? or do you spread it out over the day to lessen the shock to your system?

[gibbledygook]

Thanks Sarah,

I don't think I'll take that much of the salvia as it will just be a balancing herb. I reckon that quite a lot of us have probably rather overly coagulating blood as the body seems to think it's under some kind of immune attack and that's why these proteins have been found in the plaques. After my enzyme experience of fibrinolytics over last christmas I don't think hypercoagulation is the cause but is certainly symptomatic of the disease.

Cureo, unfortunately there isn't any info on the heat of my capsules which I bought from www.herbalextractsplus.com. It just says 100% capsicum, botanical extract 10:1. The capsules are 600mg each and I take 2 capsules in the morning and evening and if I'm feeling brave another one at lunch time. It seems to cause most problems when I don't have enough food soon after taking the capsules and then have a coffee. Over recent days my stomach seems to have settled down.

Yesterday I started a new chinese tea and this is the amount of each herb which I take on a daily basis:
2.73g rehmannia radix preparata
2.73g rehmannia radix
2.73g encommia cortex
2.73g gentiana macrophylla radix
1.36g glycyrrhiza radix
2.73g ligustri lucidi fructus
2.05g paeoniae radix rubra
2.05g curcumae longa
4.09g ganoderma
2.73g angelica sinensis
2.05g jujubae fructus

I noticed a lot of not unpleasant tingling last night in both legs and noticeable calm on the spasm front. This is a change from the last few weeks and so I suppose that the tea might be responsible. I remember thinking, hmm, something has changed last night. At this stage it's too early to say whether it's good or bad but I'm not sure I want so much ganoderma lucidum in there. As noted before this has both inflammatory and anti-inflammatory actions. I might switch back to the old tea if the tingling persists.

[CureOrBust]

Thanks gibbledygook, I think I found the one your taking, and its the same ingredient as mine (Capsicum annuum). Mine simply being 475mg / capsule. They recommend 3 tablets a day with a meal and 250ml water. I tried to find out the % content of actual "Capsaicin", but couldn't. It did lead me to The Wiki, eventually, where it became clear you should take great care when applying this directly to your nasal cavity. It is a strong lung irritant, as well as a possible stomach cancer cause. I couldn't resist, and opened one, and had a taste. It was exactly like cayenne powder (a herb I like adding to food, maybe a little hotter).

I'll let you know how I go with it.

[gibbledygook]

Good luck with it cureo, I'll be fascinated to see if you also experience any improvements in spasticity or bladder control or bowel. If you don't then I can assume that it is the combination of the herbs that I'm taking which has made such a difference.

A lot of the stuff on pubmed suggests capsaicin prevents stomach cancer. Mmm. conflicting data again. Rates of stomach cancer are low in areas where capsaicin is consumed a lot and it certainly seems effective in blocking myelenoma signaling pathways. Ho hum.

I am running out of the solgar skullcap and have replaced it with a much cheaper version from New Chapter. The pills appear to suggest they are stronger than the solgar version and have much lower weight so I am now reducing the absolute weight of the skullcap I take to 1.8g a day. I could build this up to 2.4g a day but then it's starts getting expensive. A similar event may occur shortly with astragalus as the solgar from the uk is absurdly overpriced. mmm.

ps I take up to 3g of the capsaicin, I'm not convinced 1.35g will be enough. I only weigh about 57kg...The herbal extract companies suggest quantities which are way smaller than the amounts used in chinese medicine. Also much of the research done using rats use significant quantities of the herbs per kg of body weight. I don't think I'd have noticed much from the curcumin if I'd stuck to the herb manufacturer's recommendations!

15/7/2008
Yesterday I started a different brand of astragalus from the US manufacturer, NOW. I didn't notice anything untoward except in the evening when the worst spasms I've had in ages hit me. I needed 8mg of zanaflex to get to sleep. The likely cause does seem to be the new brand of astragalus, although the day before I switched to a new brand of skullcap and a few days before then I stared the 2nd chinese tea which seemed to produce a lot more tingling. Maybe the combination of all 3 slightly new formulations was too much. It's interesting that the Now astragalus dose was virtually the same as the Solgar version and the New Chapter Skullcap was a far lower dose than the Solgar version. The spasmodic reaction to the new brands rather suggests the Solgar versions are very weak forms of the herbs.
Anyway today I decided not to take ANY astragalus and to revert to the ren shen yang rong tang tea. So I'm taking 30mg bioperine, 7.2mg of curcumin, 1.8g of skullcap, 2.4g of capsaicin and 3 mugs of ren shen yang rong tang. I'll then reintroduce the astragalus but cautiously!

16/7/2008
Well last night I had a blissful spasm free night with not even a threat of spasms. I was unusually tired this morning though and could have slept a very long time so not sure if I'm getting the fatigue thing which I've never really suffered from before. I've felt pretty fine today though so who knows. I think I'll reintroduce astragalus next week and see what happens.
I think the capsaicin is having cumulative benefits. I seem to have better bladder control in terms of controlling urgency and hesitancy. The spasticity seems much much better too. I've started to be able to put my trousers on standing up but leaning slightly against the wall. Not sure if I could do this before though, maybe it's just the layout of the new flat. Still I haven't put my trousers on standing up in ages.

[CureOrBust]

Good luck with it cureo, I'll be fascinated to see if you also experience any improvements in spasticity or bladder control or bowel. If you don't then I can assume that it is the combination of the herbs that I'm taking which has made such a difference.

Sorry to report that I have been off it (Capsaicin) for the last few days, as I had a minor relapse, so wish to wait till it all calms down and then start again. I will definitely let you know.

[gibbledygook]

Sorry to hear that Cureo. I hope that you feel better soon and that it wasn't a severe relapse nor anything to do with the capsaicin. I have noticed an increase in tingling in pre-existing sites of damage but have so much enjoyed the improved spasticity and bladder function and loose bowel that I'm happy with a bit of occasional tingling.

Annoyingly I've worked through a lot more of the PubMed database on Astragalus and I don't think I'll try that one again as it's got a lot more immune stimulatory activity than I had thought which would explain the sudden appearance of bad spasms a few nights ago. So I'm still just taking skullcap, capsaicin, curcumin and rehmannia tea. Finding herbs that downregulate MS inflammation is pretty tough! Mind you I may revisit many of the one's I've dismissed before because I do think that I must pay more attention to the humidity when considering the efficacity or otherwise of a herb. I know the astragalus must be inflammatory because relative humidity in London according to the BBC website the evening of the spasms was a low 61%. The boswellia, ashgwanda and ganoderma may still be valid, I just noticed an increase in spasticity which may have only been the humidity. Now that the capsaicin is very effectively reducing my spasticity, I believe, then I should return to them. But for the time being I'm adopting the easy root; I am now going to add NEw Chapter "zyflamend easycaps" to my regimen. This consists of the following:
rosemary, turmeric, ginger, holy basil, green tea, polygonum cuspidatum, chinese goldthread, barberry, oregano and baikal skullcap.

I reckon ren shen yang rong tang, the curcumin, the capsaicin, the skullcap and the zyflamend make quite enough medicine for the time being. Time to chill and see.

1: Biosci Biotechnol Biochem. 2007 Sep;71(9):2223-32. Epub 2007 Sep 7. Links
Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects.Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC, Peng RY.
Division of Basic Medical Science, Hungkuang University, No 34, Chung Chie Rd, Shalu County, Taichung Hsien, 43302, Taiwan.

Supercritical fluid SF-CO2 treatment of Rosemarinus officinalis L. fresh leaves under optimum conditions (80 degrees C at 5,000 psi) yielded 5.3% of extract supercritical fluid extraction (SFE)-80, in which five major active principles were identified by liquid chromatography/mass spectrometry (LC/MS), viz., rosmarinic acid, carnosol, 12-methoxycarnosic acid, carnosic acid, and methyl carnosate. Total phenolic content was 155.8 mg/ gallic acid equivalent (GAE)/g in SFE-80, which showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging of 81.86% at 0.01 mg/ml. When treated in RAW 264.7, apparent dose-dependent NO inhibition occurred at dosages of 1.56 to 6.25 microg/ml, and more drastically at 12.5 and 25 microg/ml. At 0.5 to 5.0 microg/ml, SFE-80 exhibited dose-dependent viability suppression and significant tumor necrosis factor alpha (TNF-alpha) production in Hep 3B, whereas no effect was found in Chang liver cells. Furthermore, no effect was observed in RAW 264.7 at dosages of 3.13 to 25 microg/ml, indicating that SFE-80 exhibited a noncytotoxic character. Conclusively, rosemary can be considered an herbal anti-inflammatory and anti-tumor agent.

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1: Phytother Res. 2005 Oct;19(10):864-9. Links
A pilot trial evaluating Meta050, a proprietary combination of reduced iso-alpha acids, rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia.Lukaczer D, Darland G, Tripp M, Liska D, Lerman RH, Schiltz B, Bland JS.
Clinical Research at the Functional Medicine Research Center, Gig Harbor, WA 98332, USA. DanLukaczer@metagenics.com

The aim of this open-label, 8-week observational trial was to investigate the efficacy of Meta050 (a proprietary, standardized combination of reduced iso-alpha-acids from hops, rosemary extract and oleanolic acid) on pain in patients with rheumatic disease. Osteoarthritis, rheumatoid arthritis and fibromyalgia patients were given 440 mg Meta050 three times a day for 4 weeks, which was changed to 880 mg twice a day for the subsequent 4 weeks in the majority of patients. Pain and condition-specific symptoms were assessed using a standard visual analog scale (VAS), an abridged arthritis impact measurement scale (AIMS2) and the fibromyalgia impact questionnaire. Fifty-four subjects with rheumatic disease completed the trial. Following treatment, a statistically significant decrease in pain of 50% and 40% was observed in arthritis subjects using the VAS (p < 0.0001; Wilcoxon-ranked sums) and AIMS2 (p < 0.0001), respectively. Fibromyalgia subject scores did not significantly improve. A decreasing trend of C-reactive protein, a marker for inflammation, was also observed in those subjects who presented with elevated C-reactive protein. No serious side effects were observed. These observations suggest that Meta050 at a dosage of 440 mg three times a day has a beneficial effect on pain in arthritis subjects. Copyright (c) 2005 John Wiley & Sons, Ltd.

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1: Rev Med Chir Soc Med Nat Iasi. 2007 Oct-Dec;111(4):1065-9.Links
Effects of Ocimum basilicum L. extract on experimental acute inflammation.Benedec D, Pârvu AE, Oniga I, Toiu A, Tiperciuc B.
Department of Pharmacognosy, School of Pharmacy, "I. Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca.

Our study investigated the effects of Ocimum basilicum L. tincture (1:10) in acute inflammation induced with turpentine oil (i.m. 0.6 ml/100 g b.w.) in Wistar male rats. MATERIAL AND METHODS: The results were compared with those from a positive control group with experimental inflammation and a group treated with diclofenac (30 mg/100 g b.w.). The effects were assessed by measuring total leukocyte count and differential leukocyte count expressed as a percentage, a test of in vitro phagocytosis, and the evaluation of nitric oxide synthesis by measuring the metabolites, nitrites and nitrates, and the co-product citrulline. RESULTS: Ocimum basilicum tincture significantly reduced the total leukocyte count, monocyte percentage, activation of circulating phagocytes, but had a slight inhibitory effect on NO synthesis. Compared to diclofenac, Ocimum basilicum tincture had a smaller inhibitory effect on all tested parameters. CONCLUSION: The tested Ocimum basilicum tincture has important anti-inflammatory effects on bone marrow acute phase response and a reduced one on NO synthesis

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[Sharon]

Gibbledygook -

I have been taking the New Chapter Zyflamend for over ten years - prior to my MS dx. in 2003 I started taking it for sinus and migraine headaches. Zyflamend has been recommended for arthritis. I have very little arthritis, if any, and I attribute that to the Zyflamend. I am also over the terrible sinus and migraine headaches. I take one capsule in the morning and then the PM Zyflamend at night. Hope it helps you.

I have just started taking New Chapter's Mental Clarity which is a mushroom complex with lion's mane mushroon. I have not had a chance to go back and get my references on lion's mane. Supposedly it helps with nerve repair - but, I will not post information from advertising sites, so, I need to get busy and find a few more pieces of research.

Take Care,
Sharon

[gibbledygook]

Wow - cool. I wonder what the latin name of lion's mane is. I often find that you need both names to search on Pubmed thoroughly. I saw that one of the constituents of the ren shen yang rong tang tea is polygala caudata which:

1: Neuroscience. 2007 Sep 21;148(4):915-24. Epub 2007 Aug 1. Links
Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.Naidu M, Kuan CY, Lo WL, Raza M, Tolkovsky A, Mak NK, Wong RN, Keynes R.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

We have investigated the neurite growth-stimulating properties of euxanthone, a xanthone derivative isolated from the Chinese medicinal plant Polygala caudata. Euxanthone was shown to exert a marked stimulatory action on neurite outgrowth from chick embryo dorsal root ganglia explanted in collagen gels, in the absence of added neurotrophins. It was also shown to promote cell survival in explanted chick embryo ganglia, and to stimulate neurite outgrowth from isolated adult rat primary sensory neurons in vitro. The further finding that euxanthone stimulates neurite outgrowth from explants of chick embryo retina and ventral spinal cord suggests an action on signaling pathways downstream of neuronal receptors for specific neurotrophic factors. Consistent with this, euxanthone did not promote neurite outgrowth from non-transfected PC12 cells, or from PC12 cells transfected with TrkB or TrkC, under conditions in which these cells extended neurites in response to, respectively, the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3. Western blot analysis of euxanthone-stimulated dorsal root ganglion explants showed that expression of phospho-mitogen-activated protein (MAP) kinase was up-regulated after 1 h of euxanthone-treatment. Inhibition of the MAP kinase pathway using PD98059, a specific inhibitor of MAP kinase kinase, blocked all euxanthone-stimulated neurite outgrowth. However, analysis of phospho-Akt expression indicated that the phosphatidylinositol-3 kinase-Akt pathway, another major signaling pathway engaged by neurotrophins, is not significantly activated by euxanthone. These results suggest that euxanthone promotes neurite outgrowth by selectively activating the MAP kinase pathway.

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It would be great if that is the same as lion's mane. :)

Ah - here we go from wikipedia:

Hericium erinaceus (also called Lion's Mane Mushroom, Bearded Tooth Mushroom, Hedgehog Mushroom, Bearded Hedgehog Mushroom, pom pom mushroom, or Bearded Tooth Fungus) is an edible mushroom in the tooth fungus group.

HERE WE GO!

1: Fiziol Zh. 2003;49(1):38-45.Links
The influence of Hericium erinaceus extract on myelination process in vitro.Kolotushkina EV, Moldavan MG, Voronin KY, Skibo GG.
A.A. Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev.

Myelin sheaths, wrapping axons, perform the following important functions: support, protection, feeding and isolation. Injury of myelin compact structure leads to an impairment and severe illness of the nerve system. Exact mechanisms underlying the myelination process and myelin sheaths damage have not established yet. Therefore search for substances, which provide regulatory and protective effects on the normal myelination as well as stimulating action on the remyelination after myelin damage, is of special interest. Recently it was shown that extract from mushroom Hericium erinaceus had activating action on the nerve tissue. So the aim of the present work was to study an influence of an extract from H. erinaceus on the cerebellar cells and the process of myelination in vitro. Obtained data revealed the normal growth of the nerve and glial cells with extract at cultivating. No pathologic or toxic action of the extract has been found. The cell ultrastructure was intact and similar to that observed in vivo. The process of myelination in the presence of the extract began earlier as compared to controls and was characterised by a higher rate. Thus, extract of H. erinaceus promoted normal development of cultivated cerebellar cells and demonstrated a regulatory effect on the process of myelin genesis process in vitro.

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but

1: Kaohsiung J Med Sci. 2001 Sep;17(9):461-7.Links
Antitumor and immunoenhancing activities of polysaccharide from culture broth of Hericium spp.Wang JC, Hu SH, Su CH, Lee TM.
Department of Food Sanitation, Tajen Institute of Technology, 20, Wei-Shin Rd., Shin-Erh Villege, Yen-Pu Hsing, Ping Tung, Taiwan. jicy.wang@msa.hinet.net

The fruiting body and culture broth of many edible mushrooms contain water-soluble polysaccharides. Numerous researchers have reported that these polysaccharides have immunoenhancing effects. In this study, Hericium erinaceus and Hericium laciniatum were separately cultivated in a shaker at 25 degrees C for 25 days. Polysaccharides were extracted from the culture broth. The molecular weights were larger than 1 x 10(5) k Da and their polysaccharide components were mainly glucose in H. erinaceus and galactose in H. laciniatum. Furthermore, we investigated these two purified water-soluble polysaccharides for their anti-artificial pulmonary metastatic tumor and immunoenhancing effects in ICR mice. The results revealed that both polysaccharides had significant anti-artificial pulmonary metastatic tumor effects in mice (p < 0.05). Additionally, the polysaccharide from H. erinaceus was more effective than that from H. laciniatum. However, both of the polysaccharides enhanced the increase of T cells and macrophages. The numbers of CD4+ cells and macrophages were significantly higher in the test group than in the control group (p < 0.05). From our results, no differences were found between the two purified water-soluble polysaccharides in the antitumor effects and immunoenhancing activities (p > 0.05).

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1: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Jul;14(7):427-8.Links
[Immunomodulatory function of polysaccharide of Hericium erinaceus][Article in Chinese]


Xu HM, Xie ZH, Zhang WY.
Zhejiang College of TCM, Hangzhou.

Hericium erinaceus is a Chinese herbal medicine. The Apollo oral liquid contains polysaccharide of H. erinaceus (PHE). The effects of PHE on proliferation of mice T and B lymphocytes were studied. Results showed that (1) 3-fold proliferation of thymocytes was demonstrated when PHE were administrated with Con A than Con A alone. Such effect on thymocyte was not observed when PHE was used alone. (2) Proliferation of spleen lymphocytes was also stimulated when PHE were taken together with lipopolysaccharide, which was 50% and 3 times stronger than that of using lipopolysaccharide and PHE alone respectively.

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Damm it, it seems a bit immune stimulatory. Mind you, nothing ventured, nothing gained. I think I'm going to give some of the boswellia, ganoderma and ashgawanda another go whilst paying much more attention to relative humidity in determining whether or not they are effective.

[DIM]

I already give to my wife 3 x 1gr Polygala extract daily (5:1 concentrated root extract from Yuan Zhi/Thinleaf Milkwort Root) but I can't say it works or not as it's result good or bad are non measurable!
Plus we eat at least 3 times/week Mangostine as it contains high levels of xanthones promoting nerve regeneration.

[Sharon]

A few more references on Lion's Mane -

2006.08.19] Lion's Mane Mushroom (Hericium erinaceus)
Lion's Mane Mushroom (Hericium erinaceus)
The brain tonic, Go beyond ginkgo.

Lion's Mane (Hericium erinaceus) is a mushroom with long cascading tendrils, hence the name. It is also known as "bear's head," "monkey's head," "hedgehog fungus," and "Hou Tou Gu" in Chinese. Recent studies support its traditional use for promoting healthy digestive and immune system functions. However, more promising is its ability to stimulate synthesis of the Nerve Growth Factor (NGF), which may protect nerves in the brain and body from deterioration associated with the aging process.

Bioactive constituents:
Hericenone A, B, C, D, E, F, G and H, Xylan, Heteroxylan, Heteroglucan, Proteoglycan

Bioactivities:
• Anti-alzheimer's disease: Activates synthesis of nerve growth factor (NGF) / Prevents and ameliorates senile dementia
• Anti-tumor: Enhances immune functions / Cytotoxicity
• Digestive tonic: Treats stomach and duodenal ulcers and chronic atrophic gastritis / Improves indigestion

References:
(1) H. Kawagishi et al, Tetrahedron Letters, 31(3):373 (1990)
(2) H. Kawagishi et al, Agric Biol. Chem., 54(5):1329 (1990)
(3) H. Kawagishi et al, Tetrahedron Letters, 32(35):4561 (1991)
(4) S. Furukawa et al, Kagakuto Seibutsu (Japanese), 29:640 (1991)
(5) T. Mizuno et al, Biosci. Biotech. Bioehem., 56:347 (1992)
(6) H. Kawagishi et al, Phytochemistry, 32:175 (1993)
(7) H. Kawagishi, Nippon Nogeikagaku Kaishi (Japanese), 68:1671 (1994)
(8) T. Mizuno, Food Reviews, 11 (1):173 (1995)
(9) H. Mori et al, J Appl. Glycosci., 45:361 (1998)
(10) T. Mizuno, International Journal of Medicinal Mushrooms, 1(2):105 (1999)

http://bioresearchupdate.org/informatio ... ation_id=4

The Anti-Dementia effect of Lion's Mane mushroom and its clinical application - Hericium erinaceum - Lion's Mane
Townsend Letter for Doctors and Patients, April, 2004 by Hirokazu Kawagishi, Cun Zhuang, Ellen Shnidman
Save a personal copy of this article and quickly find it again with Furl.net. Get started now. (It's free.)Introduction

Medicinal Mushrooms have become a hot item in the mass media in the last few years but the information being disseminated about them is not always scientifically accurate. Most of the studies on the efficacy of medicinal mushrooms that are available to the public are based on animal studies (usually in mice) or cultured cells. In these cases, the bioactivity of the mushroom extracts cannot always be correlated to their activity when ingested by humans--either orally or by injection.

Our research on components of Lion's Mane mushroom (Hericium erinaceum) and their biological activities in cell culture is a case where positive antidementia results in the laboratory have been confirmed by analogous results in human use. In this article, we will introduce both the results from the laboratory and their clinical application.

Conventional Treatments of Alzheimer's Disease

Alzheimer's disease is primarily a disorder of aging in which individuals become agitated and uncomprehending, with profound loss of cognitive function, ultimately requiring institutionalization. About 1 in 10 people over the age of 65 and as many as 5 out of 10 people over the age of 85 are affected. This disease is characterized biologically by the death of neurons in the forebrain, hippocampus, and cerebral cortex.

The most conventional approach to treatment of Alzheimer's disease currently in practice is to treat the symptoms caused by the death of cholinergic neurons. Four pharma-ceutical products approved by the FDA that are presently on the market work by potentiating neurotransmission at cholinergic synapses. These drugs are: Aricept[R] by Pfizer, Exelon[R] by Novartis, Reminyl[R] by Janssen, and Cognex[R] by First Horizon. None of these products, however, reverses the damage done to cognitive functioning. They simply delay further deterioration. Recently, a new drug called memantine, produced by Forest Laboratories, was approved for use by the FDA. Memantine works by blocking the receptor for the glutamate neurotransmitter whose overactivity may be responsible for the neurotoxicity of Alzheimer's disease. Likewise, its beneficial effect is only temporary.

Inducers of Nerve Growth Factor Synthesis in vitro

One of the major new approaches to the study of treatments for Alzheimer's disease concerns the search for agents that stimulate Nerve Growth Factor (NGF) production in the brain. NGF is part of a family of proteins that play a role in the maintenance, survival and regeneration of neurons during adult life. Its absence in the adult brain of mice leads to a condition resembling Alzheimer's disease.

Nerve Growth Factor itself cannot be used as an orally administered drug to regenerate brain tissue because it does not cross the blood-brain barrier. If bioactive substances with low molecular weight can be found that penetrate the barrier and induce the synthesis of NGF inside the brain, such substances may be applied as oral agents to prevent this disease. Even if these substances cannot go through the barrier, the enhancement of NGF production would be beneficial for disorders of the peripheral nervous system since NGF has a similar effect on neurons in the periphery.

We have been engaged in a study to search for NGF synthesis-promoting agents in medicinal mushrooms since 1991. We discovered a class of benzyl alcohol and chroman derivatives in the fruit body of Lion's Mane mushroom called the hericenones C-H that stimulate NGF production from mouse astroglial cells in culture. (1-18) Subsequently, we discovered another group of cyathane derivative compounds from the mycelium of the same mushroom called the erinacines A-I that also induce NGF production. (4-22) (Figure 1)

Hericenones Isolated from the Fruit Body of Lion's Mane

The hericenones were derived from Lion's Mane as follows. The fruit body of the mushroom was crushed in acetone by a blender and left for 1-2 days to allow extraction of nonpolar substances. The liquid extract was processed with vacuum filtration and the mushroom fruit body was further extracted twice by acetone. The extract was concentrated using an evaporator until 2 liters of volume was obtained, and then this was fractionated with chloroform. Ethyl acetate was added to the aqueous phase for an additional extraction.

The fractionation of the extract is an essential step for applying the compounds to the NGF assay, because there is an optimum concentration for the activation of NGF synthesis, and also most of the fractions at this stage exhibit cytotoxic activity. For separation purposes, silica gel chromatography and preparative thin layer chromatography (TLC) were employed, and two types of fractions were obtained: one with hericenones C-E and the other with hericenones F-H. Both fractions were spotted at almost the same distance on the silica gel TLC and thus separation was only possible by high performance liquid chromatography (HPLC), using an ODS column.

These compounds were the first active substances found in natural products that are as effective as epinephrine in inducing NGF synthesis in vitro. Each group of hericenones, C-E and F-H, contains a characteristic alcohol site, and each hericenone contains one of three simple fatty acids. Hericenone D demonstrated the strongest stimulating activity in synthesis of NGF from astroglial cells. The activity level of these compounds varies according to the structure of its fatty acid constituent.

Erinacines Isolated from the Mycelium of Lion's Mane

The erinacines were obtained from Lion's Mane as follows. Following 4 weeks in culture, the mycelium was extracted with 85% ethanol. The ethanol extract was concentrated, and then fractionated with ethyl acetate and water. Erinacines A-I were isolated by silica gel column chromatography on HPLC and preparative TLC.

Erinacines A-I are a series of diterpenoids, with different chemical structures from those of the hericenones, that have powerful activities in stimulating NGF synthesis. The activities of erinacines A-G in vitro are shown in Figure 2. As can be seen, all of these compounds are more potent inducers of NGF synthesis than epinephrine. The newly-discovered erinacine H stimulated 31.5 +/- 1.7 pg/ml of NGF secretion into the medium at 33.3 [micro]g/ml concentration, which was five times greater than NGF secretion in the absence of the compound. The erinacines are the most powerful inducers of NGF synthesis among all currently identified natural compounds.

Clinical Study of Lion's Mane Mushroom on Dementia Patients

Lion's Mane mushroom, therefore, contains at least two types of compounds--the hericenones and erinacines--that strongly stimulate NGF synthesis in vitro. Both of these types of substances, potentially, can cross the blood-brain barrier. The question is, do these substances work when given orally to human patients?

To answer this question, a study was done in a rehabilitative hospital in the Gunma prefecture in Japan, with 50 patients in an experimental group and 50 patients used as a control. (23) All patients were elderly and suffered from cerebrovascular disease, degenerative orthopedic disease, Parkinson's disease, spinocerebellar degeneration, diabetic neuropathy, spinal cord injury, or disuse syndrome. Seven of the patients in the experimental group suffered from different types of dementia. The patients in this group received 5 g of dried Lion's Mane mushroom per day in their soup for a 6-month period. All patients were evaluated before and after the treatment period for their Functional Independence Measure (FIM), (24), (25) which is a measure of independence in physical capabilities (eating, dressing, walking, etc.) and in perceptual capacities (understanding, communication, memory, etc.).

The results of this preliminary study show that after six months of taking Lion's Mane mushroom, six out of seven dementia patients demonstrated improvements in their perceptual capacities, and all seven had improvements in their overall FIM score (see Figures 3 and 4). A more extensive clinical study is currently underway to further investigate the findings from this small sample.

The focus of research on medicinal mushrooms until now has been primarily on their anticancer and immune-enhancing properties. The preliminary findings from the studies described above on Lion's Mane mushroom suggest that this mushroom may be a potent inducer of brain tissue regeneration. More research on this subject is clearly needed.

References

(1.) Kawagishi, H. et al. Hericenones C, D, and E, stimulators of Nerve Growth Factor synthesis, from the mushroom Hericium erinaceum. Tetrahedron Lett. 1991; 32, 4361-4564.

(2.) Kawagishi, H. et al. Chromans, Hericenones F, G, and H from the mushroom Hericium erinaceum. Phytochemistry. 1993; 32, 175-178.

http://www.curezone.com/forums/fm.asp?i=587180

Mycological Medicine
Raymond Lombardi
Robert Rountree

JANUARY 2002

Mushrooms may prove beneficial for immunity and more. Raymond M. Lombardi, D.C., C.C.N., probes the latest research on the fungi front

http://www.functionalingredientsmag.com ... te=FFNSite

I plan on continuing the Mental Clarity - at age 65 Alzeimer's scares me more than the MS.
Thanks Gibbledygook for posting the other references!

Sharon

[gibbledygook]

I must say I very much like the look of New Chapter's products. Sharon, how much do you take a day? I note that the research suggests 5g a day.