Modern research

Preclinical summary

Published preclinical data has shown that Sigesbeckia and compounds found in Sigesbeckia are:
- Analgesic
- Anti-inflammatory & reduces oedema (swelling)
- Antioxidant
- Cartilage protective
- Immunomodulatory

Clinical summary

Clinical trials conducted with Sigesbeckia have shown that:
- Subjects with rheumatoid arthritis had reductions in joint swelling and pain after taking Sigesbeckia for for one month
- Subject with osteoarthritis in the knee receiving Sigesbeckia for 5 weeks had improved signs and symptoms.

Preclinical data

Oral administration of Sigesbeckia has been shown to have a mild effect at reducing pain in the acetic acid writhing test and in the hot plate test. In the study, methanolic extracts of Sigesbeckia significant reduced stretch episodes by 32.3% in the writhing test. This about half the analgesic effect of acetylsalicylic acid (aspirin). In the hot plate test reaction time was increased by 55% over the control group (morphine positive control showed a 175% increase). The results of this study demonstrated that Sigesbeckia extract possessed centrally and peripherally medicated analgesic properties (1).

Sigesbeckia extract when used topically has been shown to have analgesic effect.  Applied topically, Sigesbeckia showed an analgesic effect in the acetic acid writhing model and the hot plate test.  The results were significant compared with the control group, but not as great as topically applied emthyl salicylate ointment (2).

References

  1. Park H-J. (2006). Antinociceptive and anti-inflammatory effect of a diterpene isolated from the aerial part of Siegesbeckia pubescensKorean Journal of Plant Research, 19(6): 660-664.
  2. Wang J et al. (2008). Anti-inflammatory and analgesic activity of topical administrations of Siegesbeckia pubescens. Pakistan Journal of Pharmaceutical Science, 21(2): 89-91.

 

There have been several papers published demonstrating the anti-inflammatory and oedema reduction effects of Sigesbeckia in the Carrageenan-induced oedema model. Oral administration of a methanolic extract of Sigesbeckia significantly reduced oedema for 2h-5h after induction (no effect observed in first hour). Carrageenan-induced oedema has two distinct phases with phase 1 (due to histamine and seratonin release) peaking after 30 minutes, and phase 2 (caused by kinins, proteases and prostaglandins), which appears after one hour. These findings suggest that Sigesbeckia inhibits phase 2 oedema (1).  Topical administration of Sigesbeckia extract in this model also showed significant reduction of oedema, with an effect comparable with peroxicam gel (2).

The findings that Sigesbeckia acts on phase 2 oedema has been confirmed by in vitro studies.  Compounds isolated from Sigesbeckia inhibit induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor alpha (TNF-a) – all of which are mediators of inflammation.  NO activates cyclooxygenase (COX-2), which in turn increases the release of pro-inflammatory prostaglandins.   In addition to this, the Sigesbeckia compounds were show to have peroxynitrite scavenging activity, a free radical created through the reaction of NO and superoxide anion that would perpetuate the inflammatory response (3, 4).

References

  1. Park H-J. (2006). Antinociceptive and anti-inflammatory effect of a diterpene isolated from the aerial part of Siegesbeckia pubescens. Korean Journal of Plant Research, 19(6): 660-664.
  2. Wang J et al. (2008). Anti-inflammatory and analgesic activity of topical administrations of Siegesbeckia pubescens. Pakistan Journal of Pharmaceutical Science, 21(2): 89-91.
  3. Kim JY, Lim HJ and Ryu J-H (2008). In vitro anti-inflammatory activity of 3-O-methyl-flavones isolated from Siegesbeckia glabrescensBioorganic & Medicinal Chemistry Letters, 18: 1511-1514.
  4. Park H-J et al. (2008).  Anti-inflammatory activities of ent-16αH, 17-hydroxy-kauran-19-oic acid isolated from the roots of Siegesbeckia pubescens are due to the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-κB inactivation.  European Journal of Pharmacology, 558: 185-193.
Extracts of Sigesbeckia have been shown to have strong antioxidant activity.  In a study examining ten different Korean herbal medicines for antioxidant activity in a lipid peroxidation system, Sigesbeckia was found to have a range of antioxidant activities. Butanolic and aqueous extracts of Sigesbeckia were show to inhibit the superoxide radical, hydroxyl radical, as well as lipid peroxide production. These extracts were also shown to inhibit the destruction of red blood cells (erythrocyte haemolysis) caused by free radicals (1).

In a thiocyanante assay, extracts of Sigesbeckia where shown to exhibit both antioxidant activity and also free radical scavenging activity. This could have benefit across a range of pathologies, including inflammation, as many reactive oxygen species are pro-inflammatory mediators (2).

References

  1. Su JD, Osawa T and Namiki M (1986). Screening for antioxidative activity of crude drugs. Agricultural and Biological Chemistry; 50 (1): 199-203. 7.
  2. Kang DG, Yun CK, and Less HS (2003). Screening and comparison of antioxidant activity of solvent extracts of herbal medicines used in Korea. Journal of Ethnopharmacology; 87: 231-236.
Oral administration of Sigesbeckia extract (100mg/kg-400mg/kg) has been shown to significantly protect joint cartilage in an osteoarthritis model. After four weeks of daily administration, there was a dose-dependent suppression of joint stiffness and improvement in histological parameters in the articular cartilage and synovial layer in a collagenase-induced osteoarthritis model. The study showed that the extract increased the expression proteoglycan, aggrecan and type-2 collagen in the knee joint. These proteins are important structural components used in the synthesis of articular cartilage. The extract was also shown to decrease the expression of protease enzymes (ADAMTS and and MMPs), enzymes responsible for the degradation of aggrecan and collagen. The extract also significantly inhibited pro-inflammatory cytokines involved in cartilage destruction, such as IL-1B, and inflammatory mediators such as prostaglandin E2 and nitric oxide. The study used celecoxib (100mg/kg) as a positive control and 400mg/kg Sigesbeckia was more effective at reducing joint stiffness (1).

In a similar study, Sigesbeckia extract was compared against ibuprofen and a placebo in a knee osteoarthritis model to explore the protective and preventative effects of the compounds on osteoarthritis. After four weeks of treatment, Sigesbeckia was shown to significantly decrease levels of the inflammatory cytokines IL-1B and TNF-a in the joint fluid compared with placebo. Microscopic examination of the joint cartilage showed that Sigesbeckia extract effectively protected cartilage cells from damage and degradation compared with the placebo group that showed clear degenerative changes in the joint cartilage (2).

References

  1. Huh et al. Therapeutic effect of Siegesbeckiae pubescens on cartilage protection in a rabbit collagenase-induced model of osteoarthritis. Journal of Pharmacological Sciences, 2008; 107: 317-328
  2. Guo LY, Hu HH and Mi JG (2006). Effect of classic formula, Xi Xian Pill, on IL-1β and TNF-α content in joint fluid and cell morphology of articular cartilage of model rabbits with knee osteoarthritis.  China Journal of Orthopaedics and Traumatology; 19 (6).
Immunoglobulin E (IgE) is an antibody that is associated with allergic reactions and diseases. Aqueous extracts of Sigesbeckia showed immune modulating effects in a dose dependant manner. The extracts inhibited active systemic anaphylaxis and serum IgE induction. The extract was shown to inhibit IL-4-dependent IgE production (1).

Whilst IgE is typically associated with allergic diseases such as asthma, food allergies and allergic rhinitis, it is also known to be elevated in various auto-immune disorders such as systemic lupus erythematosus, rheumatoid arthritis and psoriasis. Elevated IgE levels are theorised to be of importance in rheumatoid arthritis and studies have shown high levels of IgE in the sera of RA patients (2).

References

  1. Kim HM, Lee J-H, Won J-H, Park E-J, Chae H-J, Kim H-R, Kim C-H, and Baek S-H (2001). Inhibitory effect on immunoglobulin E production in vivo and in vitro by Siegesbeckia glabrescens. Phytotherapy Research; 15: 572-576.
  2. Millauer et al., 1999. High IgE in rheumatoid arthritis (RA) patients is complexed with anti-IgE autoantibodies

Clinical data

Dou (2004) examined the clinical efficacy of Xi-Tong capsules in 38 cases of rheumatoid arthritis. Xi-Tong is a TCM product made from Herba Sigesbeckia and Folium Clerodendri trichotomi and has been used historically to treat various kinds of arthritis with good efficacy. The end-points of the study was to measure improvements in joint swelling and pain as well as biochemical markers of arthritis and inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF). Study medication was taken three times daily for one month. The study reported that 76% (29 subjects) of subjects reported improvements, 38% (11 subjects) of which had significant improvement in joint pain and 62% (18 subjects) moderate improvement. 9 subjects reported no improvement in joint pain, however all subjects showed improvements in biochemical endpoints.

References

  1. Dou Y. Clinical observations on 38 cases of rheumatoid arthritis treated with Xi-Tong capsule. China Journal of Traditional Chinese Medicine; 2004; 19 (12): 752-753.
Shi (2008) examined the effects of Sigesbeckia, on its own and in combination with sodium hyaluronate, on early stage osteoarthritis of the knee. 60 patients with osteoarthritis were randomly divided into three groups and received either: Sigesbeckia together with intra-articular injection of sodium hyaluronate; Sigesbeckia on its own; or sodium hyaluronate on its own. Treatment was given over two courses, with each course lasting five weeks. Sodium hyaluronate was given once a week during each course, whilst Sigesbeckia was given twice daily. Signs and symptoms were evaluated before and after treatment, with routine haematology and biochemistry analyses. The study showed that the combination of Sigesbeckia with sodium hyaluronate had the best activity, with Sigesbeckia on its own, having superior activity to sodium hyaluronate on its own. There were no changes in routine blood, renal or liver functions in any of the groups. The study concluded that Sigesbeckia could improve the clinical efficacy of sodium hyaluronate with no signs of toxicity or side effects.

References

  1. Shi, J. Clinical observations on an ancient formula of Xi xian Wan to improve sodium hyaluronate’s efficacy in the treatment of early stage osteoarthritis of the knee.  2008; Guiyang Medical College, China.