The current standard of care for prostate cancer includes hormone therapy, radiation therapy and radical prostatectomy, each with its own set of undesirable side effects. In this regard there is an unmet need to develop strategies that can prevent or delay the development of clinical prostate cancer. One potential area involves the use of natural compounds involving botanicals.
Along these lines we have found that Nexrutine ® , a dietary supplement derived from Phellodendron amurense bark extract, has prostate cancer prevention activity. The “extract” nature of this botanical, which constitutes a blend of several active protoberberine alkaloids, allows it to target several pathways deregulated in prostate cancer simultaneously. In this review, we will emphasize the prospective translational benefit of Nexrutine ® as a chemopreventive agent for prostate cancer management. The potential of Nexrutine ® was first identified and has subsequently been most exhaustively studied with reference to prostate cancer. Therefore the focus of this review is on the use of Nexrutine ® in prostate cancer. In addition we have summarized the emerging evidence regarding the use of Nexrutine ® in other tumor models to demonstrate the potential benefits of Nexrutine ® .
Extracting the Benefit of Nexrutine ® for Cancer Prevention
The current standard of care for prostate cancer includes hormone therapy, radiation therapy and radical prostatectomy, each with its own set of undesirable side effects. In this regard there is an unmet need to develop strategies that can prevent or delay the development of clinical prostate cancer. One potential area involves the use of natural compounds involving botanicals. Along these lines we have found that Nexrutine ® , a dietary supplement derived from Phellodendron amurense bark extract, has prostate cancer prevention activity. The “extract” nature of this botanical, which constitutes a blend of several active protoberberine alkaloids, allows it to target several pathways deregulated in prostate cancer simultaneously. In this review, we will emphasize the prospective translational benefit of Nexrutine ® as a chemopreventive agent for prostate cancer management. The potential of Nexrutine ® was first identified and has subsequently been most exhaustively studied with reference to prostate cancer. Therefore the focus of this review is on the use of Nexrutine ® in prostate cancer. In addition we have summarized the emerging evidence regarding the use of Nexrutine ® in other tumor models to demonstrate the potential benefits of Nexrutine ® .
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Active Ingredients
Nexrutine is an all-natural joint and muscle supplement that is a “favorite among athletes”. One capsule is to be taken 3 times a day.All the ingredients are listed on the website.
The key ingredient is from the phellodendron tree, a plant used for centuries by traditional Chinese herbalists. Nexrutine works with the body’s natural enzymatic processes to promote comfortable movement without upsetting the stomach. It is supposed to be used after exercise to help the body recover. Nexrutine is available without the need for a prescription.
Exercise is one way of improving and maintaining our health. If you are a fitness enthusiast, you commonly experience pain and discomfort after a workout. Exercising might also cause knee pain and stiffness in the surrounding muscles in older individuals.
How Does Nexrutine Work?
According to our research, Nexrutine is made of all-natural substances and is available without a prescription, which makes it accessible to individuals suffering from body pains and discomfort. Nexrutine is derived from a bark extract from the Phellodendronamurense. Its plant-based ingredient is believed to relieve joint and muscular discomfort and aid in muscle recovery.
Some studies say that Phellodendrumamurense may prevent or delay the development of clinical prostate cancer.Apart from its pain-killing properties, it also has anti-inflammatory and anti-prostate-cancer capabilities. It is also being examined for its possible cancer-inhibiting activities in the colon and the central nervous system.
Serum collected from mice sacrificed at the 4 week and 20 week time points were assayed in duplicate using a 32 panel Mouse Cytokine/Chemokine Magnetic Bead Panel Immunology Multiplex Assay (EMD Millipore, Billerica, MA) to determine the changes in cytokine profiles. Proteins analyzed include Eotaxin/CCL11, G-CSF, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17, IP-10, KC-like, LIF, LIX, MCP-1, M-CSF, MIG, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, VEGF.
Nexrutine: Introduction
Prostate cancer (PCa) is the most common solid-tumor cancer in American males and is the second most common cause of cancer death [1]. Development of PCa spans several decades with clinical detection of PCa manifesting in patient in their 60s [2]. This long latency period provides a significant opportunity to implement chemopreventative interventions to inhibit the transition from pre-neoplastic lesions to malignant cells. It has been reported that cancer risk reduces significantly with an active lifestyle and a diet rich with phytochemicals [3, 4]. Lack of healthy activity and diets in the US point to increased incidence rates of several cancers, including PCa, compared to other countries [5].
Exercise has been shown to be beneficial in men with PCa [6–12]. However, the impact of exercise on tumor physiology are not clearly understood. A recent systematic review by Shephard found mixed results on the benefits of physical activity on PCa prevention with 45 of the 83 trials reviewed presenting diminished risk [13]. Prospective cohort studies have also found that lifelong physical activity is directly related to reduced risk of developing high grade tumors upon biopsy [14–16]. In men diagnosed with PCa, physical activity is associated with lower overall mortality and PCa mortality [17] and reduced risk of recurrence [18, 19]. Though deemed beneficial, the mechanisms by which exercise confer these benefits remain understudied.
Studying the effects of exercise on cancer prevention are difficult and time-consuming requiring years of interventional data. For that reason, relying on exercise interventions in preclinical models of cancer are favored. To date, there are few animal studies looking at physical activity and cancer that have reported beneficial outcomes [20, 21]. Voluntary wheel running has been reported to inhibit the formation of chemically induced colon [22] and breast cancer in rats [23], skin cancer [24], Panc-1 pancreatic tumors [25], and androgen-independent PC-2 prostate tumors in mice [26]. Zheng et al found that voluntary exercise inhibits the growth of prostate tumors in SCID mouse xenograft model and can enhance apoptosis in PCa tumors [20]. Esser et al., reported that 10 weeks of voluntary running at a rate of >5 km/day delayed PCa incidence and progression compared animals that ran <5 km/day [27].
While exercise interventions may be beneficial in preventing PCa, the majority of Americans fail to meet the recommended guidelines of 30 mins of activity per day or 150 mins per week [28]. This is similarly true with cancer patients, as majority of patients with PCa do not exercise regularly [29–32]. Therefore, the investigation of alternative therapies that act as an exercise mimetic can be doubly beneficial.
Nexrutine is a commercially available herbal extract from the Phellodendrom amurense, which is widely used for the treatment of inflammation, gastroenteritis, abdominal pain and diarrhea.[33] The tree is native to Asia and has been reported to contain isoquinoline, alkaloids, phenolic compounds and flavone glycosides. Recently, we have demonstrated that Nexrutine inhibits PCa cells growth implicating a role for Nexrutine in modulating growth factor signaling [34]. Currently, our understanding how Nexrutine compared to other non-toxic, non-pharmaceutical interventions, such as exercise, is missing. To that extent, we conducted a comparative effectiveness study of Nexrutine and exercise on PCa growth in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. We hypothesized that Nexrutine and exercise will have similar inhibitory effect on tumor growth through the modulation of growth and inflammatory signaling. Briefly, the results of this comparative effectiveness study suggest both Nexrutine and exercise inhibit tumor growth with both treatment groups demonstrating significantly fewer high grade tumors compared to the control group.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Study to Assess the Activity of Nexrutine® in Prostate Cancer Patients (Nexrutine)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostate Cancer | Drug: Nexrutine | Phase 2 |
Layout table for study information
Study Type :Interventional (Clinical Trial)Actual Enrollment :21 participantsAllocation:Non-RandomizedIntervention Model:Parallel AssignmentMasking:None (Open Label)Primary Purpose:TreatmentOfficial Title:Phase II Study to Assess the Activity of Nexrutine® in Prostate Cancer Patients Undergoing Surgery or Radiation TherapyStudy Start Date :July 2011Actual Primary Completion Date :March 2014Actual Study Completion Date :March 2014