Researchers identify spicy cures for painful joints

• Cinnamon, garlic, saffron, ginger, turmeric top list
• High beer consumption worsens cartilage degeneration in osteoarthritis

To treat rheumatic disease (RD) and improve patients’ disease status, researchers have explored the role of herbs and spices as adjuvant methods.

Despite advancements in the pharmacological treatment of RD in recent years, most patients do not achieve complete remission with currently available treatments. As a result, patients often seek adjuvant therapy, including dietary interventions, to improve their quality of life.

In a recent review published in Nutrients, researchers note that herbs and spices serve a prominent role in nutritional habits and medicinal purposes. Thus there is growing interest in dietary intervention with herbs and spices in the management of immune-mediated diseases, including RDs.

Most herbs and spices are abundant sources of vitamins, alkaloids, antioxidants, and noted for their remarkable anti-inflammatory and anticarcinogenic properties. The current study discusses widely-used spices/herbs in RDs, including cinnamon, garlic, saffron, ginger, and turmeric. In addition, the study’s findings provide important insights into gut microbiota and the effect of herbs and spices on rheumatoid arthritis (RA), fibromyalgia (FM), and osteoarthritis.

The progression of RDs is dependent on a combination of genetic, environmental, hormonal, and lifestyle factors. Inflammation and tissue damage are commonly observed due to the infiltration of leukocytes and proinflammatory cytokines released in affected organs.

Several studies suggest that the development of RDs like RA is due to a multifactorial pathophysiological mechanism. RA is an autoimmune and inflammatory disease characterized by autoantibodies, which are collectively described as the rheumatoid factor (RF).

Previous research shows that an imbalance in gut microbiota caused by chronic inflammation can induce RA disease progression. Numerous findings advocate that Mediterranean, vegetarian, and vegan diets help reduce pain in RA patients as compared to other diets.

In osteoarthritis (OA), tumor necrosis factor (TNF) and interleukin1β (IL-1β) promote erosion of the articular cartilage matrix. The gut microbiota also appears to be involved in the modulation of inflammation-mediated diseases like OA.

FM is a chronic condition associated with extensive pain due to inflammation, which is accompanied by high IL-6 and IL-8 levels and altered gut microbiota. Like RA and OA patients, vegetarian and vegan diets appear to ameliorate the quality of life in FM patients by reducing pain and improving sleep.

Cinnamon, garlic, curcumin, saffron, and ginger have been extensively studied for their potential use to treat inflammation in many chronic diseases, including RDs.

Cinnamon contains bioactive compounds that induce the inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), which is a transcription factor for regulating gene expression of proinflammatory genes.

Curcumin, an active turmeric compound, affects arachidonic acid metabolism and behaves similarly to non-steroidal anti-inflammatory drugs (NSAIDs). In RA patients, curcumin exhibits significant anti-inflammatory effects and reduces disease activity.

Garlic and its derivatives have been widely studied both in vitro and in vivo to evaluate its immunomodulatory and anti-inflammatory properties. Randomized controlled trials (RCTs) have also shown that garlic supplementation decreases C-reactive protein (CRP), IL-6, and TNF-α levels.

Ginger has a complex chemical composition and appears to protect against intestinal inflammation by inhibiting TNF-α-induced barrier disturbance. Ginger extract has also been found to reduce inflammation by decreasing the production of nitric oxide and prostaglandin E2 in a rat arthritis model.

Saffron and its compounds, including safranal, crocetin, and crocin, can improve disease status in RD patients by modifying inflammation, stress, pain, and antioxidant levels. However, similar to the other spices, the action of saffron was not significant enough for clinical recommendation.

Notably, the bioactive properties of these spices and herbs depend on their storage and cooking methods.

One study investigated the effect of five-gram capsules containing cinnamon, oregano, ginger, black pepper, and cayenne pepper on the gut microbiota of humans. When consumed as mixed spices, these capsules have a probiotic effect and restore gut microbiota.

In another study, the authors found that 500 mg of cinnamon significantly reduces disease activity, as demonstrated by reduced serum CRP and TNF-α, thus benefitting RA patients.

However, the RCTs conducted to date have a high risk of bias. As a result, more data and research are required to establish the health benefits of these herbs and spices.

The current study reviews the possible benefits of using herbs and spices as complementary adjuvant treatment methods for RDs, including RA, OA, and FM. Herein, the researchers highlight the antioxidant, anti-tumorigenic, anti-carcinogenic, and anti-inflammatory properties of herbs and spices while also summarising available studies investigating the effects of herbs and spices in humans with these conditions.

However, these data are insufficient for therapeutic recommendations for herbs and spices. More studies need to be conducted on supplementation and culinary use of bioactive components present in herbs and spices.

Moreover, a comparative analysis is needed between defined baseline disease activities and available pharmacological treatment with the specific herb/spice being used. This will ultimately provide insights into how to use herbs or spices or mix both in RD treatment for better disease management.

MEANWHILE, in a recent study published in the journal Nutrients, researchers determined the impact of formononetin (FNT) on the metabolism, viability, and inflammation of chondrocytes to understand the association between beer consumption and osteoarthritis risk.

What causes osteoarthritis? Osteoarthritis is a rheumatic disease characterized by the narrowing of the space in the joints due to progressive cartilage degradation. The impact of this narrowing on periarticular tissues leads to the failure of the entire joint, which subsequently causes stiffness, inflammation, pain, and loss of function. The high incidence of osteoarthritis also results in a considerable economic burden.

Although certain factors such as age, ethnicity, sex, genetic profiles, diet, mechanical stress, metabolic diseases, and inflammation can worsen the progression of cartilage degeneration, the etiology of osteoarthritis is not well understood.

Inflammatory cytokines such as tumour necrosis factor (TNF) and various interleukins (ILs) are linked to osteoarthritis progression through the release of reactive oxygen species (ROS) during oxidative stress. Inflammation and oxidative stress degrade chondrocytes and the extracellular matrix, as well as activate matrix metalloproteinases, which further degrade the cartilage extracellular matrix.

Diet is considered a modifiable risk factor for osteoarthritis, with beer consumption believed to worsen osteoarthritis. While flavonoids are some of the most active compounds in beer, the role of isoflavonoids like FNT, also found in various herbs, plants, and coffee, in osteoarthritis progression is poorly understood.

In the present in vitro study, researchers determine whether FNT impacts chondrocytes through its modulatory effects on estrogenic pathways.

Diets rich in isoflavonoids are believed to increase phytoestrogen levels, which affects the growth plate chondrocytes. FNT has a similar structure as mammalian estrogen and can bind to alpha and beta estrogen receptors (ERα and Erβ, respectively). Furthermore, FNT exerts agonistic action against the aryl hydrocarbon receptor (AhR) present on the growth plate and articular cartilages.

Murine chondrogenic cells were treated with FNT in the presence and absence of IL-1β for 48 hours, after which the cells were subjected to seven days of differentiation. Treated cells were then lysed for ribonucleic acid (RNA) extraction and subjected to a quantitative real-time polymerase chain reaction (RT-PCR).

A colorimetric 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability. Additionally, the Griess reaction was used to measure nitrite accumulation in the cells.

The protein structures for AhR, Erα, and Erβ were obtained from the Research Collaboratory for Structural Bioinformatics (RSCB) Protein Data Bank and used for the molecular docking analysis. The results of the molecular docking analysis are expressed in terms of lowest to highest Gibbs free energy for all conformations of the protein.

Low concentrations of FNT were not detrimental to cell viability and lowered the expression of genes involved in inflammation. However, high concentrations of FNT can promote catabolic responses and negatively impact chondrocytes. Furthermore, the mechanism of action of FNT on chondrocytes was not mediated through AhR or estrogen receptors.

Low concentrations of FNT between 5 µM and 25 µM, with or without IL-1β, did not impact cell viability. Other studies have reported similar results at concentrations of FNT up to 100 µM. In contrast, some studies have reported that FNT concentrations between 25 µM and 100 µM can cause apoptosis.

The anti-inflammatory activity of FNT was observed at 12.5 µM in combination with IL-1β. However, higher concentrations of FNT starting at 25 µM, with or without IL-1β, did not affect inflammation.

While isoflavonoids mimic estrogen in their modulatory effects, estrogenic pathways were not involved in the action of FNT on chondrocytes. AhR blockade experiments also reported that despite FNT being a known agonist of AhR, their impact on chondrocyte activity did not involve AhR.

Intracellular nitrite concentrations reflected the absence of oxidative stress mechanisms in FNT action, thus indicating that the effect of FNT on chondrocytes is through mechanisms other than those involving AhR, estrogen receptors, or oxidative stress.

Low concentrations of FNT were not detrimental to cell viability and had positive effects on reducing inflammation, with and without the presence of IL-1β. Furthermore, the mechanism of action of FNT on chondrocytes does not appear to involve oxidative stress, AhR, or estrogen receptors. However, high concentrations of FNT could cause catabolic responses and have a negative impact on chondrocyte viability and function.