Inflammatory breast cancer alternative medicine

The mastectomy was done in Feb 2011 and these pictures show how it looked when it healed, in August.
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Andrographolide a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis DiseaseMaria A. T Matsuda, M Kuroyanagi, S Sugiyama, K Umehara, A Ueno, K Nishi, Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.
You have probably never heard that oil based on black cumin seed is able to block the activity of cancer cells and in some cases it can eliminate specific types of these cells. Numerous studies have confirmed that black cumin seed oil also known as Nigella sativa is a very efficient treatment for different kinds of cancer even though most of these studies included lab animals.
In addition, this special oil and the extract obtained from it (thymoquinone) come with very strong health benefits in cases of different inflammatory disorders and diseases like melanoma, liver cancer, breast cancer, pancreatic cancer, stomach cancer, cervical cancer, prostate cancer, bone cancer, brain cancerand colon cancer.
Even though researchers have witnessed promising results related to the use of black cumin seed oil against different types of cancer, there are only a few studies that included human participants.
The situation is even odder because the benefits are very important and there are no indications for any kind of side effects. The research results that we will share in this article will show that using this oil for preventing and curing cancer is a very smart and efficient strategy regardless of the type of cancer.
There are many reasons for this, but there are indications that there is a political influence that discourages scientists to try this oil in people with cancer because the pharmaceutical industry can lost a lot of money. Two studies conducted 5 years ago in Saudi Arabia and China were focused on assessing literature for the use of black cumin seed and black cumin seed oil in cases of cancer. On top of that, this oil is perfectly safe and efficient in cases of cancer found in skin, cervix, breast, prostate, liver, kidneys, lungs and blood.
The scientists have found that the mechanism on a molecular level that gives this oil’s anti-cancer properties is not yet explained. But, there are studies that suggested that thymoquinone is the most important part of black cumin seed. In addition, this oil manages the so-called Akt pathway or in other words, it manages the process that controls the survival of cells no matter if we are talking about cancer or healthy cells.
Even though the anti-cancer effects of black cumin were noticed and confirmed more than 2 millennia ago, modern science has started showing interest in it recently, due to the fact that modern medicine has finally decided to test the power of traditional medicine in a scientific way.
Scientists from Egypt were focused on finding the level of protection provided by Nigella sativa and raw bee honey on cancer and oxidative stress caused by adding a powerful carcinogen in lab rats. So, once the four separate groups of lab rats were affected by the carcinogen, one group was fed with regular food, the second was fed with honey, the third with black seeds and the last group consumed a combination of organic honey and black cumin seeds. However, the lab rats that consumed a combination of black seeds and honey on a daily basis got 100% protection against cancer emergence, inflammatory responses and oxidative stress.
A study conducted two years ago in Turkey, has confirmed that black seed oil can be quite useful to individuals practicing a standard radiation treatment for different types of cancer. Turkish scientists have suggested that a huge number of patients dealing with cancer who receive this standard therapy were experiencing some serious side effects while the treatment lasted and after the treatment too. The study was focused on evaluation of the impact of irradiation and the use of black cumin seed oil on the antioxidant and oxidant system in the liver of lab rats. On the other hand, one group of lab rats got one gram of this oil per kg of body mass just 60 minutes before this radiation and got the same dose in the next ten days.
The other group that followed a radiation treatment got saline solution as a replacement for black cumin seed oil. The final results have shown that black cumin seed oil lowers the levels of oxidative stress and provides strong antioxidant effects. In other words, the use of this oil prior to radiation treatment and for ten consecutive days after the treatment, kept the rats safe from most of the side effects related to radiation. Furthermore, a study conducted four years ago in India, was focused on the impact of the use of black seed extract on lab mice receiving gamma radiation.
The experiment included elements that represent a standard human clinical environment where ordinary tissues of people suffering from cancer are treated with radiation therapy. Scientists have confirmed that the black seed extract that comes in a liquid form comes with strong protective properties against biochemical modifications and damage caused by radiation. So, the liquid that come from black seed extraction might be used in cases of cancer in humans who get radiation in order to keep them safe from oxidative stress in healthy tissues and to stop other negative side effects caused by this treatment. If everything goes well, the quality of life of patients dealing with cancer will be much higher.
After four months, the liver injury indicators, liver cancer nodules and tumor indicators were assessed in every lab rat. But, the lab rats that have taken 20 mg of this compound per kg of body mass experienced reduced indicators.
The final conclusion was that thymoquinone has a very positive effect on the treatment and healing of liver cancer due to the fact that this compound managed to inhibit the expansion of cancer cells.
A scientific study performed four years ago in Egypt, assessed anti-tumor properties of raw bee honey and black cumin seed oil on liver cancer cells through series of lab experiments. Scientists tested the antioxidant capacity of both black cumin seed extract and raw honey and the chance to use a combination of these two ingredients to get rid of cancer cells and other dangerous cells.
The tests showed that black seed extract and organic honey can lower the activity of cancer cells in the liver. A team of researchers from Saudi Arabia, confirmed that black cumin seeds were used in the regional folk medicine for healing many ailments for centuries. People were aware of the antibacterial, anti-inflammatory and antioxidant effects of black cumin seed oil for a long time.
Their study conducted two years ago was analyzing the activity of black cumin seed oil and its extract against cancer and they tested it in a lab on human cancer cells extracted from the lung. The final results have confirmed that black cumin seed extract and black cumin seed oil have the ability to radically lower the number of active cancer cells and modified the morphology of cells. In addition, the extract and oil led to changes in the size of cancer cells and they were a lot smaller than before.
Furthermore, a team of scientists from Ohio State University, revealed a scientific study three years ago that suggested that glioblastoma represents the most destructive and frequent kind of malignant brain tumor with a survival of about 1 year. The scientists highlighted the fact that the world needs more therapies for curing glioblastoma. The best part is that this compound can recognize healthy cells and avoid them while destroying cancer cells. The scientific study was focused on thymoquinone’s ability to block the proliferation of glioblastoma cancer cells located in the spinal cord and brain. As previously mentioned, thymoquinone doesn’t block the regular activity of healthy cells in these areas. What makes thymoquinone special is the fact that it can also block the actions of autophagy genes found in all cancer cells. In case autophagy is blocked, the production of cellular energy directed to cancer cells will be blocked too.
The final results is reduction of activity by tumors and protection of all organs impacted by these tumors. So, the ability of thymoquinone to block cancer cells to proliferate and the ability to block these cells from using the same cellular materials over and over again with the help of autophagy leads to a great new addition to standard therapies designed for cancer patients. A scientific study performed three years ago in Malaysia analyzed the effects of thymoquinone against cancer when this compound is used in treatment of breast cancer cells in controlled environment. The compound provided a constant capability to block expansion of breast cancer cells in cancer treatment in the long run.
Scientists in Malaysia, in a study conducted three years ago, concluded that there are more and more people who are showing interest in natural substances and compounds frequently used in folk medicine that allegedly provide anticancer effects. Black cumin seed also known as Nigella sativa is definitely one of these plants that have huge anticancer potential. The study was focused on thymoquinone, the active ingredient that comes from black cumin seeds. Scientists discovered that leukemia cell treatment with the help of thymoquinone activated apoptosis which eventually led to cell death. In other words, thymoquinone that comes from black cumin seeds is definitely an agent that should be taken into consideration when scientists design new, more effective leukemia treatments. A team of scientists from the Medical Center at the University of Mississippi noted in their study conducted 9 years ago that the chemo drug known as 5-fluorouracil remains to be the basic element of chemotherapy in cases of colon cancer. But, they have also emphasized the fact that the use of 5-fluorouracil comes with a large number of negative side effects because this drug combats both healthy and cancer cells. Their study came as a response to another research that confirmed that antioxidants can disrupt and completely block specific disease processes and activities including the ones in cancer.
This team analyzed epigallocatechin-3-gallate, a type of catechin that is found in large amounts in green tea and thymoquinone the most effective anticancer element of black cumin seeds. The main goal of this thorough study was to analyze the activity and importance of continued supply of thymoquinone obtained from black cumin seeds, the aforementioned catechin that comes from green tea and 5-FU chemo drug on the activity and modifications in the structure of colon cancer cells in humans in controlled lab terms. The final results from this scientific study revealed that catechin from green tea and thymoqunione from black seed led to radical elimination of cancer cells and disrupted their metabolic activity in a similar or even more efficient way compared to the activity of 5-FU.
In terms of morphology, cellular alterations appeared after 24-hour exposure to thymoquinone and catechin similar to the alterations provided by 5-FU chemo drug. Finally, the scientists agreed that these natural compounds may provide perfectly safe treatment in cases of colon cancer. Another scientific study conducted earlier which included Lebanese scientists, was able to determine the strong role of black cumin seed oil as a preventive agent against cancer and an efficient cancer treatment element. In the beginning of their study, these experts pointed out that black cumin seed oil was used for centuries in the Middle East, North Africa and West Asia to boost health and immune system and combat ailments. According to these scientists thymoquinone which represents the basic element of black seed is an effective natural agent for cancer prevention. Five years ago, scientists from Saudi Arabia showed that a huge number of disorders and diseases are associated with helicobacter pylori and this is especially true when it comes to peptic ulcer disease, chronic gastritis and gastric cancer. Efficient treatment of Helicobacter pylori infection with the help of antimicrobial compounds can result in regression of disorders and diseases associated with Helicobacter pylori. Black cumin seeds, a herb used frequently in folk medicine, provides strong anti-helicobacter effects. This study was conducted to assess the ability of Nigella sativa to eliminate helicobacter pylori infection in about 90 patients (non-ulcer dyspeptic).
Scientists concluded that the seeds provide helpful anti-Helicobacter effects similar to the ones received by commercial drugs, but without the side effects. Exactly five years ago, Germans scientists provided a thorough description of the modern drug known as doxorubicin.
They have pointed out that this drug is one of the basic elements of chemotherapy for cancer patients; even though it was proven that the drug is toxic for the cardiovascular system and that the effects it provides in cases of cancers highly resistant to drugs are minimal.
Several scientific studies conducted not while ago have shown the protective properties of thymoquinone, a toxin-free element of the oil of black cumin seed and they have analyzed the toxicity of doxorubicin drug.
To sum up, scientists concluded that thymoquinone compound is an enhancer for the anticancer effects provided by the chemo drug doxorubicin in specific cancer cells.
In addition, three years ago, Singaporean scientists have suggested that there is a small number of therapeutic means in cases of cancer and that cancer cells can easily adjust to these pharmaceutical agents.
Thymoquinone is a substance that comes from black cumin seed oil which has strong antitumor effects.
Researchers have realized that the treatment based on thymoquinone has the ability to hold back the growth of tumors and that the effects that we are talking about can be boosted if patients use doxorubicin chemo drug.

Scientists that work at the Wayne State University in the state of Michigan discovered that the reports related to black cumin seeds have sufficient data that guarantees extended research and studies. These experts have highlighted the need to observe and analyze the bioavailability of these seeds and Stage one toxicity profiling in individuals.
The final results from this type of research will be crucial in making progress in this area and trigger clinical trials that will involve this old natural remedy. An Omani scientist predicts the future of studies and research dedicated to black cumin seed oil. His suggestion to all scientists is to focus on thymoquinone the active ingredient of this oil. Of course, this type of research is useful and it provided very strong basis for further exploration, but it seems that it is time for clinical experiments too. There are more than one hundred scientific studies and research reports dedicated to the connection between black cumin seed oil and its most important element thymoquinone and different types of cancer. So, the question is why there aren’t many clinical trials with actual patients suffering from cancer. In addition, black cumin seed oil was discovered in the grave of one of the most famous Pharaohs – Tutankhamen which is another proof that people in Egypt respected this oil. There is archeological evidence that people back then mixed black seeds with raw honey and wax more than 3000 years ago. However, when we talk about modern treatment of cancer, this natural remedy is analyzed only in labs along with some potentially harmful highly toxic compounds. Many experts believe that there is no need for additional test tube studies or lab animal studies.
The research focused on black seed oil and its active compound thymoquinone has clearly shown that they are efficient against different types of cancer and that they don’t provide any negative side effects. What’s the Reason Behind the Absence of Clinical Research on Black Cumin Seed Oil used in Therapies? According to many specialists and experts in this field, the simplest answer is that the largest pharmaceutical companies are using their power to prevent such trials. If you take a close look at the studies and research reports you will notice that most scientists have pointed out the use of standard chemo drugs is almost ineffective in vast majority of cases. There are studies that we have mentioned before in which scientists have measured the effects of therapies which included both chemo drugs and thymoquinone and black cumin seed oil – the results show that this combination is much more efficient compared to the use of chemo drugs alone. In other cases, thymoquinone alone provided better results than chemo drugs which certainly suggest that the standard chemo drugs can be replaced with a more natural and safer remedy. Many people suffering from cancer will be glad to hear this news, but we are sure that the Big Pharma is not very excited about this.
It turns out that there is a shocking trend in this industry where pharmaceutical companies are trying to get control of all natural compounds and making them available only with prescription. Unfortunately, the Food and Drug Administration is aiding big pharmaceutical players in this scheme. For instance, they have already attempted to use vitamin B9 in its natural form, which is by the way crucial for human existence and create a folate combo in order to make a new drug that can be patented. Following this thinking pattern, Big Pharma is probably showing interest in changing their inefficient chemo drug and include some thymoquinone to boost the results of these drugs. If you are like most people then you are probably terrified from the fact that cancer patients sometimes need to destroy healthy body parts in order to feel limited effects provided by radiation or chemo therapy. On top of that, the fact that they can try, but don’t know that there is a natural remedy that can provide the same effects without side effects is even more shocking.
The data that we have presented here confirms that black cumin seed oil is able to help people avoid damage caused by radiation if it is taken right before the therapy begins and every day after treatments. It turns out that black cumin seed oil provides a strong protective support against damage caused by chemotherapy and radiation therapy and this oil is also a very powerful anticancer compound.
However, scientists and people can only speculate about the necessary amount that needs to be taken in order to get protection. What is known for sure is that the best effects from using black cumin seed oil can be felt if this oil is taken on a daily basis.
There are some people who claim that we should take between one and three tablespoons of this oil a day for different ailments.
New Research: Why Take Dangerous Statin Drugs When You Can Eat Four Of These Nuts, ONCE A MONTH Instead?
Erythrocyte sedimentation rate (ESR) in patients with chronic Rheumatoid Arthritis compared with ESR value at beginning of treatment. C Reactive protein (CRP) in patients with chronic rheumatoid disease compared with the CRP value at the beginning of treatment with Paractin®. Rheumatoid Factor (RF) in patients with chronic rheumatoid disease treated with Paractin® during 48 month. Variation on Rheumatologic stiffness in patients with chronic Rheumatoid Arthritis, treated with Paractin® during 24 month. Effect of Paractin® on Fatigue in patients with chronic Rheumatoid Arthritis, treated during 24 month.
Effect of Paractin® on pain in patients with chronic Rheumatoid Arthritis, treated during 24 month. S Handa, Standardization of the indian crude drug kalmegh by high-pressure liquid-chromatographic determination of andrographolide. W Larrick, Y Wang, Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment. Scientists have found that these seeds were known for their anti-cancer effects since ancient times. This oil and the extract that comes from it known as thymoquinone are very efficient against a myriad of serious diseases including diabetes, cancer, cardiovascular problems, kidney disease, liver disease, asthma etc.
This is a process in which our body gets rid of unwanted, unhealthy and old cells in a clean way without leaving toxins and other harmful compounds in the bodily systems. So, the lab rats that consumed only black seeds, got about 85% protection from cancer and oxidative stress.
So, the scientists exposed a small number of lab rats to one dose of strong gamma radiation. The scientists have used a group of ordinary healthy mice and a group of lab mice with tumors. The final results have revealed that black seed extract was able to protect the spleen, liver, intestines and brain from damage caused by gamma radiation in both lab mice with tumors and healthy lab mice.
It is their belief that the protective effects comes from the extract’s ability to locate free radicals and its strong antioxidant effects.
The first group received water enriched with 0.01% of this compounds and the second group received regular tap water.
The lab rats that had plain tap water experienced significant increase of the size of tumors.
I addition, this group that received thymoquinone didn’t witnessed new liver cancer nodules and the emergence of new tumors was minimal. These ingredients have also boosted the antioxidant capability of cells and triggered apoptosis. Scientists agreed that the results they got showed that black cumin seed oil and extract drastically lower the activity of lung cancer cells in humans.
Phytochemicals, compounds that occur naturally, have got a significant attention from the scientific community due to the fact that they may be able to perform powerful tumor eliminating activities. This autophagy allows constant expansion of tumor cells and it does this by keeping the production of cellular energy on an optimal level.
The yearly herb thrives in regions close to the Mediterranean Sea and in the regions of the Indian Subcontinent. The well-known ability of thymoquinone to trigger apoptosis was evaluated in leukemia cells.
Black cumin seeds block oxidative stress and they have been used by the people who live in the Middle East for hundreds of years because they can help individuals suffering from different health issues. Its ability to resist antibiotics is growing and doctors are forced to look for other options.
Each group got different combinations of amoxicillin and clarithromycin (well-known antibiotics), omeprazole which is an anti-gastric reflex medicine and regular back cumin seed oil. So far, scientists were analyzing the effects of this phytonutrient only in test tubes filled with cancer cells from human and in lab animal research with animals being exposed to different types of cancer.
As already mentioned, these studies have confirmed that this oil is not toxic and doesn’t lead to any side effects. Black cumin seed oil and black seeds were used in cases of different disorders and diseases and these remedies provided excellent results. What cancer patients need and want  is a research that includes the designing of protocols and rules for the use of this oil in a clinical environment in people diagnosed with cancer. After that, they usually add this natural compound in some of their drugs (close to patent expiration) and make a brand new drug and patent it. On the other hand, there were several studies that have confirmed the efficiency of thymoquinone alone, but obviously, these companies would not be satisfied if their drugs are replaced with inexpensive natural remedy. The truth is that there are no studies or research reports about the effects of this oil which include human clinical trials.
If you perform a brief research you will notice that there are significant number of sites that provide info about the use of this oil for cancer prevention and treatment, but there is no scientific confirmation about their recommendations.
Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysis. M Fauzi, M Sulaiman, Antiviral properties of ent-labdene diterpenes of Andrographis paniculata nees, inhibitors of herpes simplex virus type 1.
T Singh, S Bhalla, K David, et alMitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata.
These foods were added to spice up dishes and people used them as remedies and tonics for centuries.
Demographic characteristics of Rheumatoid Arthritis patients included in the double blind study of A.
Burgos1, 2[1] Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile[2] Institute of Medicine, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile1. P Rao, et alA new bis-andrographolide ether from Andrographis paniculata nees and evaluation of anti-HIV activity. M Shen, Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via 53death receptor 4 up-regulation. T Cheng, Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals. The doctor also told her about a chemo ointment they had in Germany that he heard good results from. Cynthia decided to try that first. S Wong, Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. It also grows in many other Asian countries and is used as a traditional herbal medicine in China, Hong Kong, the Philippines, Malaysia, Indonesia, and Thailand. It is an annual plant of 1-3 ft high, also known as the “king of bitters”, being the aerial parts most commonly used.
Several immunomodulatory responses of andrographolide have been observed in in vitro studies, such as reduction of iNOS, COX-2, NO, PGE2, TNF-alpha and IL-12 in macrophages and microglia. In neutrophils is able to reduce the radical oxygen species production, and Mac-1, IL-8 and COX-2 expression.

In T cells, andrographolide inhibits the expression of IL-2, IFN? and IL-6, reducing the humoral and cellular adaptive immune response. Andrographolide was able to reduce the dendritic cells maturation and their ability to present antigens to T cells.
Andrographolide administered in rodents reduced the Th2 cytokine IL-4, IL-5, IL-13 and serum immunoglobulin in an ovalbumin induced asthma model. A reduction of T cells response also has been observed in experimental autoimmune encephalomyelitis and systemic lupus erythematosus mouse model.
Several of immunomodulatory responses have been associated to the inhibition of Nuclear Factor-?B functions.
It has been demonstrated that andrographolide inhibits the nuclear translocation of the p65 subunit of NF-?B and interferes with the NF-?B binding to the DNA. Also andrographolide can reduce NFAT function in T cells and reduce the phosphorylation of signal transducer and activator of transcription-3 (STAT3) in macrophages.We propose the potential use of andrographolide in Rheumatoid Arthritis and other autoimmune diseases. This is supported by the fact that andrographolide exerts anti-growth and pro-apoptotic effects on human rheumatoid arthritis fibroblast- like synoviocytes, the main cellular constituent of pannus, that combined with a massive infiltration of lymphocytes and macrophages, invades and destroys the local articular structure. Andrographis paniculata and labdane diterpenoidsThe main and most interesting biological constituent of A.
In 1911 Gorter proved that it is structurally a lactone and named it andrographolide (in the Chinese literature it is sometimes cited as andrographis B). The properties of the compound and its diterpenoid lactone nature, as well as its stereochemistry, conformation and crystal structure were cleared by means of infrared, x, mass spectrometry and NMR analysis.
Its chemical formula corresponds to the 3,14,15,18-tetrahydroxy-5,9 H,10-labda-8(20),12-dien-16-oic acid-lactone (Figure 1).
Most recently, various epimers, geometric isomers, and rearrangement products of andrographolide have been isolated and structurally characterized [3, 4]. The pH modifies the stability of andrographolide, and hydrolysis is extremely slow below pH 7, but considerably faster on the alkaline side, producing some structural changes. Andrographolide is sparingly soluble in water; soluble in acetone, methanol, chloroform and ether. The structure of neoandrographolide (Figure 2) was described as a diterpene glucoside and its amount in the plant is around 0.5-1%.
Minor labdane diterpenesAfterwards, more than 20 other diterpene lactones, both glycosylated and not, have been described.
In other hand has been described that 14-deoxy-11,12- didehydroandrographolide possess vasorelaxant and antihypertensive [30, 31], anti-herpes [7], antioxidant and hepatoprotective [32], antithrombotic [33], antiretroviral [6], and antidiabetic properties [34]. Meanwhile 14-deoxyandrographolide exert hepatoprotective [35], uterine smooth muscle relaxant [36], immunomodulator [37], platelet activating factor antagonist [38], and vasorelaxant and antihypertensive [39] effects.
Anti-inflammatory and immunomodulatory effects of andrographolide in vitro and in vivoDifferent preparations of A.
In vitro studiesAndrographolide, shows anti-inflammatory and anticancer activities in both in vitro and in vivo.
The effects of andrographolide on two cells types that play an important role in the inflammatory processes, e.g.
Other antecedents describe a reduction of the expression of cyclooxygenase-2 (COX-2), inducible enzyme producing prostaglandins, in a human model of neutrophils [21].
In mouse peritoneal macrophages, andrographolide reduces the production stimulated by lipopolysaccharide (LPS) of two important cytokines that participate in the amplification and activation of the inflammatory process, the cytokines tumoral necrosis factor TNF? and granulocyte macrophage colony-stimulating factor (GM-CSF).
The inhibition of the release of these cytokines by andrographolide was compared to the synthetic glucocorticoid dexamethasone, showing andrographolide to have a similar effect as dexamethasone, but with a lower potency [24, 52]. Also, the effect of andrographolide on the cellular chemotaxis, a response that allows the movement of inflammatory cells to the injured tissue, show that it reduces the chemotactic migration of macrophage induced by C5a, which may contribute to its anti-inflammatory activity [53]. In local or systemic inflammatory disorders there is an enhanced formation of nitric oxide (NO) following the expression of inducible nitric oxide synthase (iNOS). The inhibition of NO formation may have therapeutic benefit in patients with inflammatory diseases as Rheumatoid Arthritis [54]. Thus, andrographolide reduces the LPS-induced iNOS and COX-2 expression in RAW264.7 macrophages [55, 56]. Additionally, andrographolide may have an effect on inflammation-mediated neurodegeneration, since it reduces the production of reactive oxygen species (ROS), TNF?, NO and prostaglandin E2 in microglia, the counterpart of macrophages in the brain [25]. Andrographolide reduces the in vitro activation of human and murine T-cells, T-cells proliferation, interleukin-2 (IL-2) and IFN? production [57-60].Interaction of leukocyte-endothelium plays a key role in the initiation and maintenance of inflammation, being the adhesion molecule ICAM-1 important in mediating leukocyte adhesion, arrest and transmigration to the inflammatory site.
In this respect, certain antecedents show that andrographolide reduces the adhesion of HL-60 cells onto human vein endothelial cells (HUVEC) and the expression of TNF?-induced ICAM-1[61, 62].
In addition, andrographolide reduces the endothelial cell proliferation, migration and invasion, suggesting a role in angiogenesis [63].
Moreover, andrographolide reduces the growth factor deprivation-induced apoptosis in endothelial cells [64].The therapeutic potential of andrographolide for the treatment of rheumatoid arthritis has been suggested by using of human rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) as a cellular model.
In vivo studiesThe anti-inflammatory activity of andrographolide has been studied in diverse in vivo inflammatory diseases models.Earlier studies with andrographolide show that it inhibited carrageenin, kaolin and nistatin-induced paw oedema. It was devoided of any ulcerogenic effect on the stomach in acute and chronic studies in rats.
Other diterpenic lactones, have shown to possess antipyretic effect in rabbits and rats with fever induced by 2-4-dinitrophenol.
Andrographolide also reduced the Th2 cytokine IL-4, IL-5, IL-13 and serum immunoglobulin [20, 52].Andrographolide also is helpfulness in the reduction of the symptoms of a mice experimental autoimmune encephalomyelitis (EAE), an animal model of human Multiple Sclerosis, by inhibiting T-cell and antibody responses directed to myelin antigens [59]. Similarly, in another model of autoimmune disease, the administration of andrographlide reduces the susceptibility, prevents the symptoms and reduces anti-nuclear antibodies and kidney damage of systemic lupus erythematous [67, 68].The potential effect of andrographolide on rheumatoid arthritis could involve angiogenesis inhibition. In fact, the development of new vessels, is important process that might facilitate the incoming of inflammatory cells into the synovium and, therefore, stimulate the pannus formation. Additionally, it is observable an increase of the levels of anti-angiogenic factors TIMP-1 and IL-2 [12]. Anti-inflammatory molecular mechanisms of andrographolideAll immunomodulatory effects of andrographolide have been attributed to modulation of different intracellular mediators, however three main mechanisms are commonly described. A first anti-inflammatory mechanism involved in the reduction of COX-2 expression by andrographolide in neutrophils comprises the modulation of the NF-?B pathway. The NF-?B is a family of transcription factors that regulate the expression of a large number of pro-inflammatory genes, such as COX-2, iNOS, TNF-alpha, IL-8 or IL-1, that are involved in the pathogenesis of Rheumatoid Arthritis. The activation of NF-?B compromises two main routes: the canonical and alternative pathways. Inflammatory receptor activation results in I?B kinase (IKK) activation, and the IKK complex phosphorylate the I?B protein, leading to its polyubiquitination.
The detailed mechanism of DNA binding inhibition indicates that andrographolide form a covalent adduct with reduced cysteine 62 of p50 subunit NF-?B, which block the binding of NF-?B to DNA [72].
The NF-?B pathway inhibition by andrographolide has been described in different cells involving in inflammatory processes such as endothelial cells [62], monocytes [73], bronchial epithelial cells [20], and dendritic cells [58].A second mechanism describes an inhibitory effect of andrographolide on iNOS and COX-2 expression in macrophages, attributable to the modulation of transcription factors AP-1 and STAT3.
AP-1 and STAT3, which are important for the production of pro-inflammatory cytokines such as IL-1?, IL-6 and IL-10, plays a major role in Rheumatoid Arthritis.
It has been reported an overexpression of activated STAT3 and high DNA binding activity of AP-1 in synovial tissue from patients with Rheumatoid Arthritis [74, 75]. In fact, andrographolide reduced the LPS-induced AP-1 DNA-binding activities, and also decreased the STAT3 phosphorylation, which is crucial for nuclear translocation and DNA binding [56]. The PI3 kinase pathway, is activated by TNF-? and IL-1, within fibroblastic synovial cells, and can activate the transcription factors NF-?B and AP-1 [77]. The use of an ERK inhibitor in the animal model of collagen-induced arthritis suppressed the antigen-specific activation of T cells [78]. Efficacy of an Andrographis paniculata composition (Paractin®) for the relief of rheumatoid arthritis symptoms: A prospective randomized placebo-controlled trialIn a prospective, double blind against placebo controlled clinical trial with chronic active Rheumatoid arthritis, the effect of a standardized patented A. Each patient received either a tablet containing 30 mg of andrographolide or a placebo 3 times a day. Andrographolide present in the extract is a potent inhibitors of NF-?B [21], a transcription factor linked to pro-inflammatory expression of several proteins such as COX-2, iNOS, and TNF-?, IL-6. Since NF-?B is involved in the pathogenesis of Rheumatoid Arthritis and other rheumatoid conditions [81], we hypothesized that A. This is closely associated with the inhibition of COX-2 [21] and the reduction of PGE2 production [25], one of the main mechanisms for the control of inflammation and pain in Rheumatoid Arthritis by NSAIDs [82]. A correlation between RF titers and clinical disease activity has been reported widely [84]. RF titers decrease with methotrexate, suggesting an indirect link with disease activity [85].
Andrographolide can reduce the TNF? production in macrophages, an effect that could be associated with the reduction of auto-antibodies. The ability of andrographolide to reduce antibody titer has also been demonstrated in other autoimmune diseases such as experimental autoimmune encephalomyelitis and lupus (see above). A reduction of immunoglobulin, such as IgM and IgA, could also be beneficial in long-term treatment because there is a positive correlation between the grade of cartilage damage in active Rheumatoid Arthritis [87] and decrease of RF. Moreover, treatment with DMARDs reduces the level of IgM and IgA in patients affected with Rheumatoid Arthritis [85].
In support of this, andrographolide reduces NFAT activity, a transcription factor linked with bone erosion [88]. None of these effects were observed in Rheumatoid Arthritis patients after 14 weeks of treatment [80].Despite, the fact that was no difference between A. BackgroundPresently, there is no specific or etiological cure for Rheumatoid Arthritis and these other rheumatoid conditions as well, and treatment aims to limit joint damage, prevent loss of function, and decrease pain.
Therapies used for these purposes include nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and corticosteroids. The American College of Rheumatology (ACR) Guidelines recommends the administration of DMARD within 3 months of diagnosis and methotrexate (MTX) as the standard treatment in monotherapy or in combination with other DMARDs [90]. MTX, as a standard therapy, induces significant improvement in the number of tender and swollen joints, pain, and functional status, in addition to physician and patient global assessment. The onset of MTX- induced improvement is generally within 3 months in the majority of patients who will eventually respond, and a plateau in the response is often reached after 6 to 12 months. However, as an anti-metabolic agent, MTX may cause adverse events such as cytopenia, serious infections, liver damage and muco-cutaneous problems. The long term use of MTX, is associated with prevalence of significant liver enzymes in aprox.
13% of the patients and 3.7% of the patients discontinue MTX permanently for liver toxicity [91]Considering that in the clinical study in patients with Rheumatoid arthritis there was a significant decrease in the group with A.
We report six case reports, with different rheumatoid arthritis conditions, that support the fact that A.
InterventionThe drug of botanical origin used for the treatment of these cases is a patented (US patent 8084495) standardized extract of A. Paractin® contains andrograpolide NLT 30%, neoandrographolide NLT 0.2% and deoxyandrographolide NLT 3%. Paractin® was supplied directly for this study and stored according to the instructions of the manufacturer. During all duration of this treatment, two tablets were given before meals three times a day. This dosage regimen was determined in previous preclinical and clinical trials with the pure compound and other commercially available A.

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