**5.5 Effect of rose hip on arthrosis and rheumatoid arthritis**

One of the larger limitations of quality of life in the elderly is osteoarthritis, which is present in more than 60% of people above 50 years of age. Osteoarthritis is often recognized in the hip, knee, spine, or hand and can reduce quality of life from simply

the pain, which occurs from joints where the cartilage is disrupted and also from the inflammation, which can follow the destruction of cartilage.

Limitations in joint movements and pain can reduce the amount of physical activity and in the long run lead to a decline in muscular mass. It becomes more difficult to climb a staircase, ride a bicycle, or to enter a car. This can result in a reduction in social activities and finally a more limited lifestyle [79]. Treatment of osteoarthritis is initially often simply to try and cure symptoms such as pain. First choice of pain cure can be painkillers such as paracetamol and/or nonsteroidal anti-inflammatory agents (NSAIDs). Later on, synthetic opioids (Tramadol) may follow [82]. However, such medication does not repair the reason for pain (cartilage which is destructed). Painkillers only treat symptoms—and on the side—they have side effects such as gastrointestinal bleeding, heart problems, and liver damage [83–87]. Literally, what health professionals are often doing is that they place a bucket on the loft, to catch the water dripping from the destroyed roof instead of repairing the hole in the roof by placing a new roof tile. So, any herbal remedy, which reduces pain and even better also supports the restauration of cartilage, is of high interest in osteoarthritis.

Rheumatoid arthritis is a chronic, inflammatory, and autoimmune disease affecting the joints and also shortening life. Most common symptoms are pain, swollen joints, stiffness of joints, and loss of function. The initial treatment is usually diseasemodifying antirheumatic drugs (DMARDs) often supported with pain killers such as paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs), which as earlier described have side effects. So, any herbal remedy, which can reduce pain and even better support repairment of the body, is of value also in rheumatoid arthritis.

Osteoarthritis is the disease in which rose hip (*Rosa canina*) has been tested the most, as we were able to find a total of six randomized, placebo-controlled, double-blinded clinical studies performed in humans. Five of these studies tested a powdered version of *Rosa canina* subspecies Lito, containing seeds as well as shells dried at very low temperature [23]. The background for this methodology was, as earlier discussed, that heating to more than about normal body temperature might destroy active ingredients in seeds and shells. These five studies focused on osteoarthritis of the hip, knee, and hand. The sixth study was focusing on osteoarthritis of the knee and was based on a product consisting of powdered shells only originating from Chile without any seeds added. The temperature during the preparation procedure was not given, but presumably it was high as most products from Chile are heavily heated [23]. Finally, there was a meta-analysis based on the shell and seed version of rose hip. There were two studies on rheumatoid arthritis, both placebo-controlled and based on the seed and shell version of rose hip.

If not stated, the treatment period was invariably 3 month and the dosage 5 gram daily of powdered rose hip containing seeds and shells served in capsules.

When focusing on osteoarthritis using the combined seed and shell powder, there was a significant reduction in reported pain and stiffness in all five studies [60, 67, 88–90]. In addition, there was also an improvement in general well-being and daily activity such as climbing a staircase, visiting the toilet, or entering a car. The improvement in daily activity was possibly the result of less pain and less stiffness in joints [60, 67, 88–90]. It is interesting to note that in four of the five studies, one study [60] was presented as a dose finding study, indicating dose dependency, there was a significant reduction in the consumption of rescue medication such as paracetamol, tramadol, or NSAIDs [67, 88–90]. This is of some interest as the volunteers in all studies were told not to change the consumption of rescue medication—even though they did so.

See details in **Figure 7**.

#### **Figure 7.**

*Delta change in the consumption of 500 mg paracetamol tablets. The delta change is the delta value of the first fourteen days minus that of the last 14 days of a three-month treatment period.*

When testing the shells only powder (2.225 gram daily), there were no impacts on what patients reported on symptoms such as pain, stiffness, daily activity, or quality of life and neither on the consumption of rescue medication. However, some improvements in knee function could be detected when using gait analyzing in a motor function laboratory [63].

A meta-analysis indicated that the Lito rose hip subspecies significantly reduced pain in osteoarthritis and that the effect size was better than what was observed for paracetamol [91] and comparable to what was seen for NSAIDs [92, 93]. Details are shown in **Figure 8**.

One of the two studies on rheumatoid arthritis only lasted for 1 month, and results were not conclusive [94]. The other study lasted for 6 month, and after 3 month there was a statistically significant improvement in daily activity scores, which was maintained also after 6 months of treatment. After 6 months, there was a further statistically significant improvement in patients as well as doctor's evaluation of disease severity and in quality of life using SF questionnaires [61].

In summary: There are strong indications that the combination of seeds and shells from subspecies of *Rosa canina* exerts a reduction in pain and an improvement in daily

#### **Figure 8.**

*Effect size of Rosa canina (Lito) right panel, to that of NSAIDs (mid panel) and that of paracetamol (left panel). It should be recognized that the Effect Size of rose hip is close to three times higher than that of paracetamol.*

function in osteoarthritis and that the same remedy can be of some benefit to sufferers of rheumatoid arthritis [61, 91]. Other subspecies including subspecies from *Rosa rugosa* can have similar effects; this however remains to be established. From the present evidence it seems clear that both shells and seeds are needed as a study on shellsonly did not show any impact on the pain and discomfort reported by patients [63].

However, the biochemical background for the beneficial effects of *Rosa canina* still remains to be fully elucidated. It was encouraging to note that C-reactive protein (CRP) fell in two studies on osteoarthritis [59, 60]. In a study on rheumatoid arthritis, there was a significant reduction in sedimentation rate, an inflammatory marker [61]. Again, no such changes in inflammatory markers were seen testing shells-only powders [62, 63]. From the insight we have today, it seems that a certain molecule, a galactolipid named GOPO, which acts as an anti-inflammatory agent, is important [95]. The high amount of natural vitamin C, present in *Rosa canina*, and easily absorbed [96] can play an important role for restoring collagen. Also, linoleic and alpha-linolenic acids, which contribute to the COX-1 and COX-2 inhibitory effects observed in rose hip together with triterpene acids, can add some clarification [97, 98]. And finally, the reduction in the synthesis of MMP-1 responsible for the breakdown of collagen can play an important role [81].

#### **5.6 Rose hip for managing renal disturbances**

The kidneys can be damaged in diseases such as diabetes and hypertension. In addition, the formation of stones in the kidneys gives rise to painful and dysfunctional condition. Acute kidney injury is defined as a disorder with disruption of kidney function leading to renal failure. Two major reasons for acute kidney injury are inflammation and oxidative stress. A correlation between a reduction in oxidative stress and a reduction in renal failure was observed in a study where rats with induced acute kidney injury were fed *Rosa canina* [99]. Similar results involving ameliorating renal failure were also observed in another group of rats treated with *Rosa laevigata* [100], as well as in rats suffering diabetes [101, 102].

Prevention strategies for avoiding calcium oxalate nephrolithiasis (kidney stones) are important and on demand. *Rosa canina* extracts have been tested and shown to reduce the number of calcium oxalate calculi and prevent nephrolithiasis in treated rats [103]. On the other hand, human studies for the effects of rose hip treatment on kidney dysfunction are lacking. However, it was encouraging to note that serum creatinine, a marker of kidney function, significantly improved in a human study with *Rosa canina* Lito [59].

#### **5.7 Rose hip in liver protection**

As we earlier stated from our search on folk medicines, rose hip has been claimed to act as a detoxifier. So, are there any indications that rose hip can support the liver? Hepatic injury (liver toxicity) is often characterized by lipid peroxidation, the production of free radicals, and a reduction in antioxidant enzyme activity. Among blood analyses, which can describe to what extend the liver is injured, there are serum alanine transaminase (ALT) and serum aspartate transaminase (AST). Due to our lifestyle, which for many include overeating, consumption of high amounts of alcohol and for some people also sometimes the consumption of different versions of medicine—foods and food supplies, which can protect the liver, has drawn increasing attention. In a study on rats where liver injury was induced, *Rosa canina* restored the abovementioned marker enzymes as well as histopathological alteration caused by the injury. The authors of the paper found a reduction in ALT and AST as the result of treatment and suggested that *Rosa canina* may exert its liver restoring capacity from its content of antioxidants and phenolic compounds [104]. In another study on diabetic rats testing the impact of *Rosa rugosa* on accumulation of fat in the liver, there was also a reduction in ALT and AST as the result of treatment together with a reduction in fat accumulation in the liver [105]. In a study on humans, consuming 45 gram daily of powdered *Rosa canina* from the subspecies Lito containing seeds and shells, given for 1 month, did not affect ALT [59]. However, treating 40 g daily of pure seed powder from the same subspecies for a full 3-month period resulted in a statistically significant drop in ALT (personal communication, K. Winther). This may indicate that also compounds related to rose hip seeds can be important when discussing the protection of the liver, and possibly 1 month of treatment is too short a timeframe when testing the impact of an herbal remedy on liver protection in humans.

In conclusion: From the literature available, it seems like different families of rose hip can be of interest when developing a treatment or a diet, which exerts some liver protection.

#### **5.8 Rose hip for treating skin disorders and aging**

Chronic inflammatory skin disorders (dermatitis) are common in humans of all ages, and we all get facial wrinkle as we get older than 50 years of age. Anti-inflammatory

remedies can reduce the numbers and depth of wrinkles. The two main factors that determine aging of the skin are a) aging associated with time and b) aging resulting from exposure to UV, also known as "photo aging." The combination of these two factors results in loss of functionality of the skin as a barrier against "the outer world." Therefore, dryness, wrinkles, and spots (melanomas) occur. Consequently, protecting the aging skin with anti-inflammatory agents and antioxidants is very important [106].

An extraction of the root of *Rosa multiflora* was recently reported to improve dermatitis in an animal model via COX-2 inhibition. *Rosa multiflora* root extract that is rich in tannins was also shown to be antiallergic by lowering the number of eosinophil leucocytes in another animal model [107, 108]. Interestingly, quercetin isolated from *Rosa canina* was found to lower the melanin content in mouse melanoma cells, while oral administration of rose hip reduced skin pigmentation in guinea pigs [109, 110].

One human study demonstrates that a *Rosa canina* subspecies can influence skin wrinkles, the moisture of the skin, as well as skin elasticity [80]. The study was double-blinded and randomized, lasted 8 weeks, and included 34 volunteers. The effects of *Rosa canina* Lito were compared with a well-known antiwrinkle remedy, Astaxanthin. After 8 weeks of treatment, there was a significant reduction in the depth of crow feet wrinkles as the result of oral rose hip treatment. Similarly, skin moisture and skin elasticity were also significantly improved. The impact was comparable with that of Astaxanthin, which is a strong antioxidant containing the carotenoid pigment. Carotenoid pigment is also found in the rose hip preparation used [23], which is a strong antioxidant too, and rich in several xanthins and able to inhibit the synthesis of MMP-1, an enzyme responsible for the breakdown of collagen [81]. Such strong antioxidant may help to protect collagen and elastin from free radicals formed by UV-induced oxidation, which is responsible for skin aging [109, 110]. It is indeed interesting to note that the actual version of rose hip has been documented to improve collagen [81] and symptoms of osteoarthritis [67, 89–91]. In osteoarthritis as well for the skin, collagen plays a very central role. Another aspect of rose hip impact on the skin is GOPO and its anti-inflammatory property [59, 97]. GOPO was shown to inhibit the chemotaxis of neutrophils and the production of interleukins [59]. Inflammation is a key factor of particular interest as UV radiation is known to result in cell destruction and inflammation. Anti-inflammatory agents therefore have their place as a treatment. It should also be remembered that rose hip seeds and oil from these seeds are used to restore burn injury and restore scars in South America. As earlier stated, seeds from rose hip are also rich in poly unsaturated fatty acids (PUFA), among them linoleic acid and alpha linolenic acid [99], both major constituents of the barrier function of the epidermis [111, 112].

When human erythrocytes are stored in a blood bank, they can normally be stored for up to 5 weeks before the hemoglobin starts to leak out through the erythrocyte membranes as an indicator that the membranes are now disintegrating (getting older). Eighteen healthy volunteers were given 45 gram daily of rose hip powder (Lito) containing seeds and shells for 4 weeks and compared with a group of controls. It was shown that the leak of hemoglobin from red cells, in these volunteers, when stored in a blood bank, was significantly reduced because of treatment with rose hip [80]. Details are shown in **Figure 9**. This was evident after 14 days of treatment and remained for the entire treatment period. This indicates that cell membranes from human erythrocytes, when stored in a blood bank, survive longer before they disintegrate if

#### **Figure 9.**

*Hemoglobin is leaking out through the erythrocyte membrane as the result of disintegration over time (aging) of the membrane. If human volunteers are treated Rosa canina this leak of hemoglobin is lowered indicating that membranes are now more resistant to disintegration.*

volunteers have been treated rose hip the latest month before blood sampling. There is improved longevity of the red cell membranes as the result of rose hip treatment.

In summary: rose hip can influence wrinkles, moisture, and elasticity of the skin, as well as add to the longevity of red blood cells stored in a blood bank. The mechanism behind these properties is believed to be dependent on the antioxidant activity, as seen in the ability of rose hip to suppress the activity of matrix metalloproteinase 1 (MMP-1) that is involved in the breakdown of extracellular matrix and in particular, tissue remodeling. The result of MMP-1 suppression is also supportive to collagen. Anti-inflammatory capacity and certain fatty acids that are present in the seeds and shells are also thought to play an important role here.

#### **5.9 Rose hip and diseases related to the gastrointestinal tract**

Antiulcerogenic activity from "folk remedies" has often been reported, and in this connection, *Rose canina* L is also mentioned [113]. An antiulcerogenic effect from *Rosa canina* extracts was discovered in a rat model. It was later shown that *Rosa canina* can prevent gastric mucosa erosion and the associated hemorrhagic ulcer formation [114]. Extracts from the leaf of *Rosa canina* were also reported to have significant antidiarrheal activity, as well as significantly reduce the intestinal transit time in another animal study [115]. In a clinical trial on humans suffering either Morbus Crohn or Ulcerative colitis, it was documented that the combined seed and shell powder from *Rosa canina* (Lito) significantly lowered symptoms from Morbus Crohn but not symptoms from Ulcerative colitis [116]. One reason for that phenomenon can be that the rose hip version used in the experiment could inhibit neutrophil chemotaxis [59]. Excessive neutrophil activity is involved in the pathogenesis of Morbus Crohn.

In conclusion: Rose hip is interesting when focusing on the gastrointestinal tract, especially by impacting the gastro microbiome. However, more clinical studies in humans need to be available before making any conclusions.
