Novel Chinese herbal medicine JSK improves spinal cord injury outcomes in rats

Contact: Daphne Watrin d.watrin@iospress.nl 31-206-883-355 IOS Press

Findings published in Restorative Neurology and Neuroscience

Amsterdam, NL, August 19, 2013 – A new study published in Restorative Neurology and Neuroscience demonstrates that Chinese herbal medicine Ji-Sui-Kang (JSK), given systemically for three weeks after injury in rats, improved locomotor function, reduced tissue damage, and preserved the structure of neural cells compared to control rats. The report also includes data showing that JSK may first act to reduce inflammation and cell apoptosis and death, and boost local oxygen supply while, later on, it appears to restore function and promote tissue regeneration.

Although Chinese herbal medicines have traditionally been used for a variety of ailments, the rationale for their use relies more on anecdotal evidence than the results of modern-day controlled experiments.

“A number of anecdotal reports from Chinese medicine practitioners indicate that treatment with a novel herbal formulation, JSK, for periods of one week or three months improved functional recovery,” explains co-lead investigator Shucui Jiang, MD, PhD, head of the Hamilton NeuroRestorative Group at McMaster University in Hamilton, Ontario, Canada. “Our present study provides an important and necessary foundation for further studies of JSK.”

In this study rats began JSK treatment immediately after undergoing spinal cord injury. Within 7 days, hindlimb locomotor function was significantly better in JSK-treated rats compared to those receiving only saline. JSK-treated rats continued to have better motor function than controls throughout the 21-day test period and treated animals appeared to support their weight better and have more coordinated movements.

When the investigators looked at histological samples of the spinal cord, they found that the architecture of the spinal cord was better preserved in JSK-treated animals and the size of the injured area was significantly smaller 7 days after injury. JSK-treated animals also showed more intact axons and myelin in the injured areas compared to controls. Other encouraging signs were less deposition of fibrinogen in the injured areas of JSK-treated animals, a decrease in pro-inflammatory COX-2 expression, and fewer cell deaths at the lesion site (as measured by caspase-3 staining).

JSK also increased the expression of growth associated protein 43 (GAP43), a marker of neuronal development and axonal regeneration, and neuroglobulin, a protein found in cerebral neurons that is thought to help neurons survive and recover after trauma. “Our data suggest that JSK may enhance tissue recovery by reducing cell growth inhibitors and by promoting the proliferation of cells within the injured spinal cord,” says co-lead investigator Michel P. Rathbone, MD, CHB, PhD, Professor, Division of Neurology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Other findings suggest JSK might help protect against injury caused by damage to spinal cord blood vessels. For instance, JSK increased vascular endothelial growth factor (VEGF), a protein involved in the formation and growth of blood vessels, down-regulated clotting-associated genes, and promoted factors that contribute to vasodilation.

The authors say that JSK targets multiple biochemical and cellular pathways that may help protect against the primary traumatic injury as well as subsequent secondary injuries that evolve over time.

The authors do not disclose the complete herbal composition of JSK for proprietary reasons. Some of its ingredients include Ginseng, Rhizoma (chuan xiong), Glycyrrhizae Radix (gan cao), Paeoniae Alba Radix (bai shao) and Cinnamomi Cortex (rou gui).

Light exposure during pregnancy key to normal eye development

Contact: Nick Miller nicholas.miller@cchmc.org 513-803-6035 Cincinnati Children’s Hospital Medical Center

Contact: Jason Bardi jason.bardi@ucsf.edu 415-502-4608 University of California, San Francisco

CINCINNATI – New research in Nature concludes the eye – which depends on light to see – also needs light to develop normally during pregnancy.

Scientists say the unexpected finding offers a new basic understanding of fetal eye development and ocular diseases caused by vascular disorders – in particular one called retinopathy of prematurity that can blind premature infants. The research, led by scientists at Cincinnati Children’s Hospital Medical Center and the University of California, San Francisco (UCSF), appears online Jan. 16 ahead of print publication.

“This fundamentally changes our understanding of how the retina develops,” says study co-author Richard Lang, PhD, a researcher in the Division of Pediatric Ophthalmology at Cincinnati Children’s Hospital Medical Center. “We have identified a light-response pathway that controls the number of retinal neurons. This has downstream effects on developing vasculature in the eye and is important because several major eye diseases are vascular diseases.”

Lang is a principal investigator on the ongoing research along with project collaborator, David Copenhagen, PhD, a scientist in the departments of Ophthalmology and Physiology at UCSF. The scientists say their current study, conducted in mouse models, includes several unexpected findings.

“Several stages of mouse eye development occur after birth,” says Copenhagen. “Because of this, we had always assumed that if light played a role in the development of the eye, it would also happen only after birth.”

But researchers in the current study found that activation of the newly described light-response pathway must happen during pregnancy to activate the carefully choreographed program that produces a healthy eye. Specifically, they say it is important for a sufficient number of photons to enter the mother’s body by late gestation, or about 16 days into a mouse pregnancy.

Researchers were also surprised to learn that photons of light activate a protein called melanopsin directly in the fetus – not the mother – to help initiate normal development of blood vessels and retinal neurons in the eye.

One purpose of the light-response pathway is to suppress the number of blood vessels that form in the retina. These vessels are critical to retinal neurons, which require large amounts of oxygen to form and to function. When retinopathy of prematurity occurs in infants, retinal vessels grow almost unchecked. This continued expansion puts intense pressure on the developing eye and in extreme cases causes severe damage and blindness.

The research team led by Lang and Copenhagen conducted several experiments in laboratory mouse models that allowed them to identify the light-response pathway’s specific components and function.

Mice were reared in the dark and in a normal day-night cycle beginning at late gestation to observe the comparative effects on vascular development of the eye. The researchers verified the function of the light response pathway by mutating an opsin gene in mice called Opn4 that produces melanopsin, in essence preventing activation of the photo pigment.

Both mice reared under dark conditions from late gestation, and those with mutated Opn4, exhibited nearly identical promiscuous expansion of hyaloid vessels and abnormal retinal vascular growth. The unchecked vascular growth was driven by the protein vascular endothelial growth factor (Vegfa). When the light response pathway is properly engaged, it modulates Vegfa to help prevent promiscuous vascular growth, according to researchers.

The melanopsin protein is present in both mice and humans during pregnancy. Lang said the research team is continuing to study how the light-response pathway might influence the susceptibility of pre-term infants to retinopathy of prematurity and also be related to other diseases of the eye.

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First author on the study was Sujata Rao, PhD, a member of Lang’s laboratory team. Funding support for the research came in part from the National Institutes of Health (NIH AR-47363) and the Abrahamson Pediatric Eye Institute at Cincinnati Children’s.

About Cincinnati Children’s:

Cincinnati Children’s Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report‘s 2012 Best Children’s Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children’s is one of the top two recipients of pediatric research grants from the National Institutes of Health and a research affiliate of the University of Cincinnati College of Medicine. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org.

About UCSF:

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. http://www.ucsf.edu

Macular Degeneration drugs may do More harm than good ( anti-VEGF drugs )

Scripps Research Institute Study Suggests Caution and Further Studies on Drugs Used to Treat Macular Degeneration

LA JOLLA, CA – October 24, 2012 – Millions of people with “wet” macular degeneration are prescribed a class of medication known as anti-VEGF drugs. But now scientists at The Scripps Research Institute (TSRI) have found that a drastic reduction of VEGF activity may do more harm than good.

In the new study, the researchers deleted the gene for the blood-vessel growth factor VEGF, which has been implicated in stimulating abnormal blood vessel growth in a range of cancers and eye diseases, from cells in the retinas of adult mice. The results showed that without VEGF a large subset of light-sensing cells lost their main blood supply and shut down, causing severe vision loss.

“It’s becoming clear that VEGF has a critical function in maintaining the health of the retina, and we need to preserve that critical function when we treat VEGF-related conditions,” said TSRI Professor Martin Friedlander, MD, PhD, senior author of the new study, which appears in the November 2012 issue of the Journal of Clinical Investigation.

Major Target for Drug Developers

VEGF (vascular endothelial growth factor) has long been a major target for drug developers. Tumors often overproduce VEGF to stimulate local blood vessel growth and thus keep their fast-dividing cells well supplied with oxygen and nutrients. Low-oxygen conditions in the eyes of elderly or diabetic individuals also can trigger the overproduction of VEGF, resulting in a vision-destroying bloom of abnormal, leaky retinal blood vessels.

Several anti-VEGF drugs (such as Lucentis® (ranibizumab), Macugen (pegaptanib), Eylea® (aflibercept) and Avastin® (bevacizumab)) are already in use, and dozens more are in clinical trials against cancers and common eye disorders such as wet macular degeneration.

However, to date there have not been extensive studies on the effects of such drugs on the normal role of VEGF, in part because it is hard to generate adult animals that lack the VEGF gene. When the gene is removed from the embryos of mice, in a standard“knockout” experiment, the mice fail to develop normally and die before birth.

New Insights

In the new study, Friedlander laboratory postdoctoral fellows Toshihide Kurihara, MD, PhD, and Peter D. Westenskow, PhD, found a way to delete the major VEGF gene from mice after the animals had grown to adulthood. To determine VEGF’s role in the retina, they confined the gene deletion to the animals’ retinal pigment epithelial cells, which nourish and repair the retina and are a major retinal source of VEGF. The result suggests that VEGF does have a crucial function in the adult retina.

“Only three days after we knocked down the gene, we observed the complete deterioration of the choriocapillaris, a layer of capillaries that is a major supplier of nutrients to the outer retina, the location of the rod and cone photoreceptors,”said Kurihara.

Nearby light-sensing cone cells, which are specialized for detecting color and fine detail in visual images, also rapidly lost their function, causing pronounced vision loss in the mice. Seven months after the knockdown of the VEGF gene, the retinal damage and vision loss were still evident. “The deterioration seems irreversible if VEGF is not present,” said Westenskow.

Rod cells, which support low-light and peripheral vision, were not affected by the VEGF-gene deletion. The researchers note that cone cells may be more vulnerable because they are unusually active metabolically and may be unable to withstand a significant decrease in blood supply. Cone cells also bear receptors for VEGF molecules and thus may require direct VEGF stimulation to remain healthy. In any case, even if only cone cells died and rod cells were spared, a patient would experience severe vision loss. “You’d be defeating your purpose if you dried up the abnormal blood vessel growth but at the same time killed off the cone cells,” said Friedlander.

Paths for Future Research

Whether such side effects are happening with existing anti-VEGF treatments is unclear. While these assessments are possible, but they have been considered prohibitively expensive and invasive.

Friedlander, however, now believes such studies are necessary and plans to conduct such assessments in eye-disorder patients—who typically receive direct injections of anti-VEGF drugs to their eyes—to determine whether the drugs are causing these adverse side effects. He notes that the evaluations may be particularly necessary for a new class of anti-VEGF drugs recently approved for use in the treatment of age-related macular degeneration—drugs that are much more potent and persistent than previous anti-VEGF agents.

Fortunately, anti-VEGF drugs are not the only possible strategy for treating pathological blood vessel growth, as the new study makes clear. VEGF-related tumors and eye conditions also involve the overproduction of low-oxygen signaling proteins known as HIFs. The team found that deleting the genes for these HIFs in retinal cells largely prevents blood vessel overgrowth in a standard mouse model—without affecting the normal-level production of retinal VEGF or causing eye damage.

“In light of the present findings, other strategies for treating these eye conditions could be a possibility,” Friedlander said. “Conceivably, an anti-HIF treatment could also be combined with an anti-VEGF treatment, allowing the dose of the latter to be lowered significantly.”

The Friedlander lab, in collaboration with the laboratories of David Cheresh, PhD, and Michael Sailor, PhD, of the University of California, San Diego, has also been exploring the potential utility of inhibiting microRNAs that regulate angiogenic genes further upstream to VEGF. This work is being supported by a $10 million grant from the National Eye Institute and could lead to the development of antagonists that avoid the off-target effects of VEGF inhibitors.

In addition to Friedlander, Kurihara and Westenskow, other contributors to the study, “Targeted deletion of Vegfa in adult mice induces vision loss,” were Stephen Bravo and Edith Aguilar, both of TSRI. For more information on the paper, see http://www.jci.org/articles/view/65157.

The study was supported in part by grants from the National Eye Institute of the National Institutes of Health (EY-11254, EY-021416), the Lowy Medical Research Institute, the Manpei Suzuki Diabetes Foundation and The Japan Society for the Promotion of Science.

About The Scripps Research Institute

The Scripps Research Institute is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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For information:                     Office of Communications                             Tel: 858-784-8134                                     Fax: 858-784-8136 press@scripps.edu

 

http://www.scripps.edu/news/press/2012/20121024friedlander.html

Green tea may affect prostate cancer progression

2009 study posted for filing

Contact: Tara Yates
tara.yates@aacr.org
267-646-0558
American Association for Cancer Research

PHILADELPHIA – According to results of a study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, men with prostate cancer who consumed the active compounds in green tea demonstrated a significant reduction in serum markers predictive of prostate cancer progression.

“The investigational agent used in the trial, Polyphenon E (provided by Polyphenon Pharma) may have the potential to lower the incidence and slow the progression of prostate cancer,” said James A. Cardelli, Ph.D., professor and director of basic and translational research in the Feist-Weiller Cancer Center, LSU Health Sciences Center-Shreveport.

Green tea is the second most popular drink in the world, and some epidemiological studies have shown health benefits with green tea, including a reduced incidence of prostate cancer, according to Cardelli. However, some human trials have found contradictory results. The few trials conducted to date have evaluated the clinical efficacy of green tea consumption and few studies have evaluated the change in biomarkers, which might predict disease progression.

Cardelli and colleagues conducted this open-label, single-arm, phase II clinical trial to determine the effects of short-term supplementation with green tea’s active compounds on serum biomarkers in patients with prostate cancer. The biomarkers include hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostate specific antigen (PSA). HGF and VEGF are good prognostic indicators of metastatic disease.

The study included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery — four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, according to Cardelli. The time of study for 25 of the 26 patients ranged from 12 days to 73 days, with a median time of 34.5 days.

Findings showed a significant reduction in serum levels of HGF, VEGF and PSA after treatment, with some patients demonstrating reductions in levels of greater than 30 percent, according to the researchers.

Cardelli and colleagues found that other biomarkers were also positively affected. There were only a few reported side effects associated with this study, and liver function remained normal.

Results of a recent year-long clinical trial conduced by researchers in Italy demonstrated that consumption of green tea polyphenols reduced the risk of developing prostate cancer in men with high-grade prostate intraepithelial neoplasia (HGPIN).

“These studies are just the beginning and a lot of work remains to be done, however, we think that the use of tea polyphenols alone or in combination with other compounds currently used for cancer therapy should be explored as an approach to prevent cancer progression and recurrence,” Cardelli said.

William G. Nelson, V., M.D., Ph.D., professor of oncology, urology and pharmacology at the Johns Hopkins Kimmel Cancer Center, believes the reduced serum biomarkers of prostate cancer may be attributable to some sort of benefit relating to green tea components.

“Unfortunately, this trial was not a randomized trial, which would have been needed to be more sure that the observed changes were truly attributable to the green tea components and not to some other lifestyle change (better diet, taking vitamins, etc.) men undertook in preparation for surgery,” added Nelson, who is also a senior editor for Cancer Prevention Research. However, “this trial is provocative enough to consider a more substantial randomized trial.”

In collaboration with Columbia University in New York City, the researchers are currently conducting a comparable trial among patients with breast cancer. They also plan to conduct further studies to identify the factors that could explain why some patients responded more dramatically to Polyphenon E than others. Cardelli suggested that additional controlled clinical trials should be done to see if combinations of different plant polyphenols were more effective than Polyphenon E alone.

“There is reasonably good evidence that many cancers are preventable, and our studies using plant-derived substances support the idea that plant compounds found in a healthy diet can play a role in preventing cancer development and progression,” said Cardelli.

 

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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and nearly 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes six major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Anti-cancer ( Avastin ) drug damages brain vessels

Contact: Hema Bashyam hbashyam@rockefeller.edu 212-327-7053 Journal of Experimental Medicine

The cancer drug Avastin (bevacizumab) is used to treat advanced bowel cancer in combination with chemotherapy. This drug targets a protein called VEGF (vascular endothelial growth factor) that stimulates blood vessel growth. Avastin inhibits the growth of tumors by cutting off their blood supply, which deprives them of oxygen and other nutrients. In a small percentage of patients, however, Avastin can cause neurological side effects ranging from headaches and blurry vision to potentially fatal seizures and brain swelling.

The new study reveals that VEGF normally protects the specialized cells that create a seal between the brain and spinal column and thus prevent fluid from leaking into the brain. When VEGF was blocked in mice, these cells died and the animals developed brain swelling. The authors suspect that Avastin’s side effects in humans may be caused by a similar phenomenon. Why these symptoms occur in only a few patients is not yet known

reposted at request from 2008

Triphala and Its Active Constituent Chebulinic Acid Are Natural Inhibitors of Vascular Endothelial Growth Factor-A Mediated Angiogenesis

Triphala churna (THL) is a combination of three fruits that has been used for many years in India for the treatment of various diseases. There are now reports which indicate that THL can inhibit growth of malignant tumors in animals. However, the mechanisms by which THL mediates its anti-tumor actions are still being explored. Because vascular endothelial growth factor-A (VEGF) induced angiogenesis plays a critical role in the pathogenesis of cancer, we therefore investigated whether tumor inhibitory effects of THL or its active constituents are through suppression of VEGF actions. We herein report that THL and chebulinic (CI) present in THL can significantly and specifically inhibit VEGF induced angiogenesis by suppressing VEGF receptor-2 (VEGFR-2) phosphorylation. These results are of clinical significance as these inexpensive and non-toxic natural products can be used for the prevention and treatment of diseases where VEGF induced angiogenesis has an important role

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Results and Discussion

There are now studies which indicate the therapeutic efficacies of THL in tumor bearing animals [7][10]. However, there is still no report indicating the effects of THL on VEGF induced angiogenesis [7][10]. We at first determined whether single oral dose of 100 mg/kg of THL could inhibit VEGF (250 ng) mediated angiogenesis in vivo in a well established mouse matrigel plug assay model [14][17]. This dose of THL was particularly selected as this dose demonstrated the highest efficacy in human malignant tumor bearing mice [10]. In addition, we also did not observe any significant changes in the complete blood count, hepatic enzymes, cholesterol, blood sugar, blood urea nitrogen (BUN) and serum creatinine level with this dose of THL in mice when compared to normal controls (data not shown). On day 8, THL untreated plugs containing VEGF appeared dark red, Masson’s trichrome staining (endothelial cells stain red and the matrigel stain blue) and CD31 immunostaining demonstrated higher levels of endothelial cells in these VEGF containing THL untreated plugs (Fig. 2 A–D). In contrast, on Day 8, plugs containing VEGF removed from animals treated with THL for 7 days were pale in color and the endothelial cells were also significantly less in numbers (Fig. 2A–D). Similar results were observed in control plugs without VEGF removed from animals untreated with THL (Fig. 2A–D). These data confirmed that oral administration of THL could significantly inhibit VEGF induced angiogenesis in vivo.

Furthermore in vitro studies have indicated the anti-VEGF actions of GA and EA, two constituents of THL [26], [27]. Since the bioavailability of these two compounds following ingestion of either fruits containing these two acids or in pure forms is poor [11], [12], [28], [29], [30] and because we had observed significant suppression of VEGF induced angiogenesis following oral administration of THL in our in vivo model (Fig. 2), we therefore examined the plasma level of another major constituent of THL, CI following oral feeding of mice with THL. The plasma concentration of CI reached to 1952.67 ng/ml (2.04 μM) at 20 min after gavaging the mice with a single dose of THL (100 mg/kg) containing 6.8 mg of CI as detected by LC-MS/MS.

Because VEGF mediates its angiogenic actions by stimulating proliferation, migration, tube formation and endothelial cell permeability [1][4], therefore in order to investigate whether THL could specifically inhibit these functions of VEGF in endothelial cells, we initially determined the non-toxic concentration of THL to be used for our in vitro experiments in HUVEC by examining the cytotoxic effects of various concentrations of THL (20–80 μg/ml) that were previously reported to inhibit tumor cell growth in vitro [9], [10], [31]. In addition, we also determined the effect of 2 μM of CI on the viability of HUVEC as this concentration of CI was detected in the plasma of mice after orally feeding them with the VEGF inhibitory dose of THL (100 mg/kg). Our results indicated 40 μg/ml of THL to be the highest non-toxic concentration of THL and 2 μM CI had no effect on cell viability (Fig. 3A, B). Accordingly, we selected 40 μg/ml of THL and 2 μM of CI for further in vitro experiments.

We next examined the effects of non-toxic concentration of THL (40 μg/ml) and CI (2 μM) on VEGF induced proliferation, migration, tube formation and permeability in HUVEC. Our results indicated significant inhibition of VEGF (20 ng/ml) induced proliferation (Fig. 3 C, D), migration (Fig. 4 A–D) and tube formation (Fig. 5A–D) by these cells after treatment with THL or CI. In addition, THL and CI also significantly inhibited VEGF induced permeability in HUVEC (Fig. 5E). It is to be noted here that THL (40 μg/ml) or CI (2 μM) alone had no effects on proliferation, wound healing, tube formation and permeability of the endothelial cells (data not shown).

Furthermore as these actions of VEGF is mediated mainly through its VEGFR-2 [1][4], therefore to elucidate the molecular mechanisms by which THL or CI inhibited VEGF functions, we investigated the effects of THL (40 μg/ml) and CI (2 μM) on VEGF (20 ng/ml) induced VEGFR-2 phosphorylation in HUVEC. Our results demonstrated that THL or CI significantly inhibited VEGF induced phosphorylation of VEGFR-2 (Fig. 5F).

Since our previous in vitro data suggested that THL and CI could significantly inhibit the important steps of VEGF induced angiogenesis (Fig. 3, 4, 5), therefore, we determined the effects of THL (40 μg/ml) and CI (2 μM) on VEGF mediated angiogenesis in CAM assay [19], [24], [25]. All observations were made on Day 4 after addition of these compounds. There was no evidence of angiogenesis or inflammation on addition of the vehicle (PBS) in which THL or CI were dissolved (Fig. 6A, E). However, striking angiogenesis was evident after exposure to 250 ng of VEGF (Fig. 6B, E). On the contrary, significant inhibition of VEGF induced angiogenesis was observed following exposures to 40 μg/ml of THL or 2 μM of CI (Fig. 6C, D, E). THL or CI alone did not induce any inflammation nor had any effects on blood vessel formation (data not shown).

Taken together our results for the first time demonstrated that THL or CI present in THL can significantly inhibit VEGF induced angiogenesis via suppression of VEGFR-2 actions. Moreover unlike the other constituents of THL such as GA and EA, the plasma level of CI reached considerably after oral intake of THL and this level of CI in turn could significantly and specifically inhibit the actions of VEGF in vitro. These results thus suggest that CI present in THL mediate the anti-VEGF effects of THL in vivo and is also a potent inhibitor VEGF functions. However, there may be other untested constituents of THL, which may also possess anti-VEGF activities.

Finally, VEGF mediated neovascularization plays an important pathogenic role in various diseases [1][3]. The presently available anti-VEGF drugs not only have serious toxicities, but are also very expensive [32][34]. This necessitates development of newer and effective non-toxic and inexpensive anti-VEGF agents. Our present study suggests that THL or CI may fulfill this promise in future

LINK to Full Study

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0043934