Life Extension Magazine May 2018
Plant Compounds that Reduce Joint Cartilage Loss
By Corey Pine
Osteoarthritis reduces joint mobility, induces persistent pain, and diminishes quality of life.1-3
Drugs aimed at pain relief are only effective in about half of those who use them.4
An alternative has been identified with three botanical extracts that do more than mask symptoms: They may repair damage caused by the disease.
Osteoarthritis causes loss of cartilage that sets off a vicious cycle of inflammation. This contributes to destruction of joint cartilage and worsening of the condition.
Compelling data reveals how three plant extracts can reduce damage to cartilage and bone in arthritis-afflicted joints while suppressing pain and inflammation.4-6
Research findings suggest that early intervention with these botanical combinations may help prevent cartilage damage,4-6 making them a unique way to beneficially modify joint structure and function.
Powerful Pain Relief
significant reductions in knee pain
compared with baseline, but the cutch
tree/white mulberry extract combination
showed significantly greater relief
compared with placebo and glucosamine/
chondroitin by end of study at Week 12.4
Scientists at Central Michigan University set out to study the effects of cutch tree (Acacia catechu) and white mulberry (Morus alba) extracts in people with osteoarthritis.4
The purpose of their study, published in 2017, was to determine if cutch tree/white mulberry extract can alleviate discomfort and improve function in adults with osteoarthritis of the knee. This is one of the most common sites of disabling osteoarthritis.
The study included 135 adults with osteoarthritis of the knee who were randomly assigned to receive one of three treatments:
1. A placebo.
2. Glucosamine (1,500 mg/day) and chondroitin (1,200 mg/day).
3. Cutch tree/white mulberry herbal extracts (400 mg/day).
All subjects took their assigned capsules for 12 weeks.4
Initially, all three treatment plans produced relatively good pain relief, with significant decreases in knee pain over the 12-week period.4
But by day 56, subjects taking the herbal combination had significantly greater reduction in pain compared with placebo or the glucosamine/chondroitin groups (Figure 1 on this page). Overall, the herbal combination group experienced less knee pain and stiffness.4
The potential of pain relief is an exciting prospect for anyone suffering from osteoarthritis. But the most exciting finding from this study came from a urine test which indicated that the herbal combination could not only protect against joint damage, but may also be able to stop the progression of the disease.
Reducing Osteoarthritis-Induced Joint Damage
significant difference in urinary
CTX-II levels between the changes
for cutch tree/white mulberry extract
combination and placebo after
12-week product use (P = 0.029).
To assess the effects of cutch tree/white mulberry on joint structure, this same study looked at urinary levels of C-terminal crosslinking telopeptide (CTX-II). This test measures the breakdown product of collagen and serves as a useful indirect biomarker of joint destruction.4
To understand the CTX-II marker, it is important to know how osteoarthritic damage degrades joint structure. As cartilage gradually wears down there is a reduction in joint smoothness along with the impact-cushioning that cartilage provides.
In the osteoarthritic process, more CTX-II is released as the joint undergoes more damage. Higher levels of CTX-II in the urine indicate larger amounts of joint damage.7-9
Subjects taking the cutch tree/white mulberry extracts showed a significant decrease in their urinary CTX-II levels, indicating that the herbal combination was protecting the joint against damage, and could reduce the risk of osteoarthritis progression over time.
In sharp contrast, urinary CTX-II levels rose sharply in the placebo group, and there was little change in the glucosamine/chondroitin recipients.4
No serious adverse events were reported during the study, and lab tests of metabolic function and toxicity remained normal in all groups.4
This study showed that the herbal combination enhanced pain relief, reduced joint stiffness, and, most importantly, contributed to improved joint protection and reduced cartilage breakdown, compared with placebo and glucosamine-chondroitin.
Studies on the individual ingredients give us more insight into how they bring about such dramatic benefits.
Cutch Tree Extracts Cut Inflammation
The cutch tree (scientifically, Acacia catechu) is a thorny South Asian tree in the same family as beans and other legumes.4 The bark and heartwood are rich in catechin, a flavonoid molecule that is also found in green tea and has multiple bioactive properties.
One of the most impressive aspects is its anti-inflammatory activity. This includes inhibiting major pro-inflammatory signaling molecules such as COX-2, 5-LOX, various interleukins, and tumor necrosis factor-alpha. Cutch tree also suppresses the “master inflammatory promoter” complex called NF-kappaB.4,10
The FDA has approved the extract as a natural flavoring substance, an indication of its safety and widespread use.4
White Mulberry Contributes to Joint Integrity
White mulberry (Morus alba) comes from root bark of the tree. It has longstanding status in traditional medical systems for its use against infections, high blood sugar, ulcers, pain, and inflammation.4
The root and bark of the mulberry tree is rich in bioactive compounds, particularly flavonoids and stilbenoids, which have been shown to have pain- and inflammation-relieving properties, and help preserve the integrity of joints.11,12
Dual Protection for Joints
Bottom: White Mulberry
While their individual healing properties have been well documented, the combination of cutch tree and white mulberry extracts is relatively new. It is the result of a comprehensive research program that inspected more than 12,000 botanical sources in search of the optimal properties for joint protection.13
This dual herbal combination has been extensively evaluated in human, animal, and basic laboratory studies for its ability to fight the inflammation, pain, and, most importantly, joint degradation seen in osteoarthritis.13
The first study described in this article was a human study from 2017.
Additional findings published in early 2017 showed this dual herbal formula was effective in reducing cartilage breakdown in laboratory rats. This study showed:
1. Reduced breakdown of cartilage.
Scientists examined the impact of cutch tree and white mulberry on the breakdown of proteoglycans, essential components of the cartilage matrix that cushions and lubricates joints. They found these two plant extracts reduced cartilage breakdown by 31%-54%, depending on the dose used.6 This demonstrated the mixture’s cartilage-protecting abilities in the laboratory model, which we’ve now seen echoed in the 2017 human study.
2. Reduced pain sensitivity.
In a rat model of osteoarthritis, researchers administered the cutch tree/white mulberry herbal combination.6 Using standard techniques for detecting pain behavior in animals, the researchers found reductions in sensitivity to pain of 17% in the first week, which rose steadily through week five to a 40% reduction in sensitivity to pain.6
Once again, this echoes the pain relief demonstrated in the human study, with the ability to relieve pain increasing the longer the supplement is used.
3. Minimized bone damage.
In addition to this reduction in pain sensitivity, there were significant improvements in joint cartilage integrity. And when the joints were dissected and directly examined by pathologists, bone damage was found to be minimal in the areas underlying the protective cartilage layer in joints.6
Bone damage is what ultimately leads to joint failure and the need for surgical replacement, so this finding got the attention of joint experts and orthopedic surgeons.
The finding of reduced bone and cartilage destruction in arthritis joints represents a disease-modifying effect that has never been shown with any of the pain relievers commonly used to treat osteoarthritis, including NSAIDs and opiates. This may represent an advance in the management of arthritis as a potentially reversible disorder.
As Effective as Ibuprofen
Finally, another animal study revealed that the herbal combination’s pain-relieving properties are strikingly similar to those of another standard pain-reliever: ibuprofen, which is commonly sold in drugstores as Advil®.
For the study, scientists used a rat model of pain in which a harmless compound (carrageenan) is injected into the paw, inducing temporary pain and swelling. The results of that study confirmed that the herbal extracts were superior to no treatment in improving pain and reducing swelling, while the highest doses tested were similar to ibuprofen in ability to improve pain and reduce swelling.14
This study (as well as one other) showed that the cutch tree/white mulberry extract combination inhibited the enzymes COX-1, COX-2, and LOX—all of which manufacture pro-inflammatory signaling molecules, demonstrating one important mechanism of action for the supplement combination.13,14
Chinese skullcap (Scutellaria baicalensis) is rich in a compound called baicalin, with known anti-inflammatory properties that complement those in cutch tree.
Animal and basic lab studies have established that the combination of Chinese skullcap and cutch tree acts as a dual inhibitor of inflammatory signaling molecule production and activity, and is capable of significantly reducing pain and swelling.5,15-19
One study, conducted by pain-relief experts in Montreal, included 52 subjects (40-75 years old) with osteoarthritis of the knee or hip severe enough to require treatment.20
Subjects were randomly assigned a placebo, 200 mg/day of celecoxib, or one of two doses of the combination herbal supplement (250 or 500 mg/day). Study subjects were followed-up at 30, 60, and 90 days for pain, stiffness, functional impairment, and physical function using standard measurement scales.
Study results showed that at days 30 and 90, both doses of the dual-action supplement were significantly more effective at reducing pain than celecoxib. The higher, 500-mg/day herbal dose proved superior to celecoxib already at day 30, and was superior to placebo by the 90-day endpoint of the study. By contrast, celecoxib was not significantly more effective than placebo at days 30 or 90.
For reducing stiffness, both herbal supplement doses were effective at all time-points compared with baseline measures.20 Similarly, both doses were superior to placebo for stiffness relief at 30 and 90 days, while no changes compared with baseline stiffness were seen in either the placebo or the celecoxib groups.
Functional impairment was significantly reduced in the 500 mg herb-supplement group compared to celecoxib or placebo at all time-points, with a significant improvement compared with baseline as well, an effect not seen in either the celecoxib or placebo groups.
Finally, scores for physical function were significantly improved compared to baseline for both doses of the herb-supplement combination and for celecoxib at all time-points, while by day 90, the supplement was superior to celecoxib.
Osteoarthritis brings with it not only pain, soreness, and stiffness, but progressive joint degradation, loss of mobility, and eventually the possibility of a knee or hip replacement.
No current treatments are able to slow or reverse that cartilage breakdown. Pain medications are effective in less than 50% of osteoarthritis sufferers.
The combination of three healing herbs—Chinese skullcap, cutch tree and white mulberry—has the potential to change the osteoarthritis landscape.
Studies show that each extract provides anti-inflammatory and pain-relieving properties. Together, the herbal combinations have been shown to reduce markers of cartilage degradation and joint destruction.
As with any approach that offers prevention and relief of symptoms, the earlier you start, the better the long-term protective effect.
This highlights the importance of not waiting until arthritis pain becomes debilitating. By then the damage has largely been done.
Cartilage degradation can be prevented in vulnerable knee and hip joints. Regular use of these plant extracts may be started as soon as joint stiffness and pain arise—and can potentially ward off years of misery.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437-41.
- Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163-96.
- Global Burden of Disease Study C. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743-800.
- Kalman DS, Hewlings SJ. The Effects of Morus alba and Acacia catechu on Quality of Life and Overall Function in Adults with Osteoarthritis of the Knee. J Nutr Metab. 2017;2017:4893104.
- Yimam M, Brownell L, Pantier M, et al. UP446, analgesic and anti-inflammatory botanical composition. Pharmacognosy Res. 2013;5(3):139-45.
- Yimam M, Lee YC, Wright L, et al. A Botanical Composition Mitigates Cartilage Degradations and Pain Sensitivity in Osteoarthritis Disease Model. J Med Food. 2017;20(6):568-76.
- Garnero P, Piperno M, Gineyts E, et al. Cross sectional evaluation of biochemical markers of bone, cartilage, and synovial tissue metabolism in patients with knee osteoarthritis: relations with disease activity and joint damage. Ann Rheum Dis. 2001;60(6):619-26.
- Mazieres B, Garnero P, Gueguen A, et al. Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort. Ann Rheum Dis. 2006;65(3):354-9.
- Charni N, Juillet F, Garnero P. Urinary type II collagen helical peptide (HELIX-II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2005;52(4):1081-90.
- Yang JA, Choi JH, Rhee SJ. Effects of green tea catechin on phospholipase A2 activity and antithrombus in streptozotocin diabetic rats. J Nutr Sci Vitaminol (Tokyo). 1999;45(3):337-46.
- Chan EW, Lye PY, Wong SK. Phytochemistry, pharmacology, and clinical trials of Morus alba. Chin J Nat Med. 2016;14(1):17-30.
- Yimam M, Lee YC, Moore B, et al. UP1304, a Botanical Composition Containing Two Standardized Extracts of Curcuma longa and Morus alba, Mitigates Pain and Inflammation in Adjuvant-induced Arthritic Rats. Pharmacognosy Res. 2016;8(2):112-7.
- Unigen Inc. Amlexin: A New Approach to Joint Protection. Unpublished data.2015.
- Yimam M, Lee YC, Jiao P, et al. UP1306, a Botanical Composition with Analgesic and Anti-inflammatory Effect. Pharmacognosy Res. 2016;8(3):186-92.
- Altavilla D, Squadrito F, Bitto A, et al. Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages. Br J Pharmacol. 2009;157(8):1410-8.
- Burnett BP, Jia Q, Zhao Y, et al. A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. J Med Food. 2007;10(3):442-51.
- Tseng-Crank J, Sung S, Jia Q, et al. A medicinal plant extract of Scutellaria Baicalensis and Acacia catechu reduced LPS-stimulated gene expression in immune cells: a comprehensive genomic study using QPCR, ELISA, and microarray. J Diet Suppl. 2010;7(3):253-72.
- Unigen Inc. Univestin: Advanced Joint Comfort. Unpublished data.2015.
- Yimam M, Brownell L, Hodges M, et al. Analgesic effects of a standardized bioflavonoid composition from Scutellaria baicalensis and Acacia catechu. J Diet Suppl. 2012;9(3):155-65.
- Sampalis JS, Brownell LA. A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin. Nutr J. 2012;11:21.