Apitherapy - an overview | ScienceDirect Topics

Bee Venoms
Apitherapy (the use of bee products) has long been used in patients with the chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. Venom from the honey bee (Apis mellifera) is often injected at a traditional acupuncture point (Zusanli), and its analgesic and anti-inflammatory actions have been shown both in animal models and human trials of autoimmune arthritis and multiple sclerosis.16 The anti-inflammatory effects of bee venom are at least in part mediated by melittin through the inhibition of the cyclooxygenase COX-2 and of the production of superoxide by neutrophils, both major players in the maintenance and amplification of inflammation in the joints during rheumatoid arthritis. However, mellitin also exhibits hemolytic and cytotoxic activities against mammalian cells and needs to be modified before it can be safely developed into a drug.
Bombolitins from the bumble bee Megabombus pennsylvanicus degranulate mast cells and induce the release of histamine and other bioactive compounds. It may therefore have therapeutic use.1
Apitherapy
Apitherapy178,179 is the use of bee stings to treat specific chronic inflammatory disorders180 including rheumatism181 neurologic disorders,182 vascular disorders, gastrointestinal disorders,183 or allergic disorders.184 (This modality must not be confused with specific Hymenoptera venom immunotherapy to desensitize patients who have experienced anaphylaxis from the stings of these insects, discussed in Chapter 78.)
This therapy grew out of anecdotal reports of bee stings that cured bronchitis and arthritis. The treatment regimen consisted of live bee stings once daily or three times a week applied to the spine, presumably correlating with the involved joint or along acupuncture “trigger” points. Pressure was then applied by the thumb to the point of pain. After the first weeks of treatment, some patients experienced exacerbation of their disease in a so-called reactive stage, considered as essential and reflecting activation of the immune system. When a specific (unidentified) level of resistance is reached, therapy is commonly stopped. Treatment was individualized in accordance with clinical response and was stopped if anaphylaxis occurred.
In the 1930s, commercial forms of injectable bee venom (Apiven, Venapis, Lyovac, Imminin, Apicosan) became available, with 0.1 mg of pure dry bee venom equated to one bee sting. Active research in the United States and other countries stopped in the early 1950s with the advent of effective antibiotics and corticosteroids. A recent resurgence in studies on the beneficial effects of bee stings, however, has been attributed to the availability of water-soluble fractions, interaction with metalloproteinases, and mellitin (mellitinin),180,185,186 an antiinflammatory agent known to be 100 times stronger than cortisone in suppression of cytokine production.187 In clinical practice, adverse effects such as anaphylaxis have been one of the major issues, as well associated risk for development of other complications such as hepatotoxicity.188
Application to Clinical Practice
Patients who are interested in BVT may be informed that there is no evidence of BVT efficacy for disease-modifying or symptomatic effects in MS. It may be helpful to provide information about therapies for which safety and efficacy studies have been performed. Because of the risk of optic neuritis, periorbital BVT should be avoided. Patients may be told that BVT can rarely cause side effects, including anaphylaxis. Because of possible allergic reactions, patients who choose to use BVT should have an epinephrine kit available and should know how to use it.
Neuropathic and neuroischemic ulcer treatment
Debridement
Conservative debridement may be necessary using minimal sharp debridement, however debriding agents such as honey or larval therapy should be considered dependent on vascular status [29].
Offloading
This is arguably the most important aspect of the treatment of neuropathic foot ulcers that are at risk of infection, hospitalization, and amputation. The first choice for plantar forefoot or midfoot ulcers in a people with diabetes should be a nonremovable knee-high offloading device [28]. In the event of patient intolerance, or contraindications such as ischemia or infection a removable knee-high device could be used, or an ankle-high offloading device [28]. Appropriately, fitting footwear combined with felted foam can be considered as the fourth-choice offloading treatment [28]. The IWGF, 2019 Guidelines provides detailed evidence-based advice for correct offloading at all stages and classification of DFU [2].
Surgical offloading
Interventions for metatarsal head and digital ulcers can be considered such as Achilles tendon lengthening (ATL), metatarsal head (MTH) resection, osteotomy, arthroplasty, ostectomy, exostectomy, external fixation, flexor tendon transfer or tenotomy, and tissue fillers such as silicone or fat. These procedures aim to provide a more permanent offloading of elevated mechanical stress; however, surgery comes with increased risk [28].
In an earlier prospective, controlled, group-comparison trial in piglets (n=44) with induced enteropathogenicEscherichia coli diarrhoea, traditional acupuncture at Du-1, ST-36, BL-20, Ren-12 and ST-25 produced the best results in comparison to the groups treated with electro-acupuncture or antibiotics. There were too many groups given the number of cases. Hwang et al, Am J Vet Res 1988
Du-3 Rats treated with electro-acupuncture at Du-3, BL-54 and BL-60 15 minutes after a standardised spinal cord injury at T8, showed a marked improvement (regarding both morphology and functioning) three days post-operatively compared to rats not treated with acupuncture. However, none of the beneficial effects occurred in rats given acupuncture treatment 24 hours after spinal cord injury. Politis et al, Acupunct Electrother Res 1990
Du-4 A Turkish prospective, randomised, non-blinded, controlled group-comparison trial (n=24) investigated the efficacy of acupressure at Du-4, Du-15, Du-20, BL-23, BL-28, BL-32, HE-7, HE-9, ST-36, SP-4, SP-6, SP-12, Ren-2, Ren-3, Ren-6, KID-3 and KID-5 on enuresis compared to oxybutynin given to the control group. Acupressure was administered to 12 patients by the parents. While treatments in both groups were successful, complete recovery was significantly higher in the acupressure group (83.3%) compared to the control group (58.3%). Yuksek et al, J Int Med Res 2003
Du-11 Electro-acupuncture at Du-11 and Du-16 prior to, during and after an experimentally induced transient ischaemia in gerbils suggests the protective influence of these points. They seem to suppress both glutamate release and reperfusion injury following the ischaemic insult. Pang et al, Am J Chin Med 2003
A Chinese experimental trial (n=40) investigated the effect of acupuncture at Du-14 and P-6 on driving performance during a three-hour driving simulator test. The acupuncture group showed a significantly better driving performance and a decrease in driving fatigue, compared to the untreated control group. Li et al, Accid Anal Prev 2004
A Chinese prospective, randomised, controlled, non-blinded trial (n=40) investigated the effect of acupuncture at Du-14 and P-6 on heart rate and driving performance during a three-hour driving simulator test. The acupuncture group showed a significantly decreased activation of the sympathetic nervous system and increased parasympathetic activity compared to the untreated control group. Li et al, Eur J Appl Physiol 2003
A Chinese prospective case study (n=50) reports the successful treatment of perennial allergic rhinitis by applying 10% Cantharides extract at Du-14 and P-6. The results showed an effective rate of 88%. The allergic nasal mucosa provocative test of the treated group improved after the treatment, the number of eosinophils and basophils in nasal secretion decreased and the serum total IgE also reduced significantly. Tang et al, Zhongguo Zhong Xi Yi Jie He Za Zhi 1995
Du-15 → T.B.-8; Du-4
Du-16 → Du-11
Du-20 → T.B.-8; G.B.-4, ST-8; Du-4; LIV-3; HE-7, L.I.-4
A Chinese prospective randomised controlled single-blinded group-comparison trial (n=50) investigated the effect of a standardised acupuncture protocol, used either on its own or accompanied by needling of Du-20, Du-26 and HE-7 (either singly or in combination) on vascular dementia in hemiplegic patients. Clinical symptoms were observed and scales such as HDS-R, ADL and functional activities questionnaire (FAQ) used for assessment. The group additionally treated with Du-20 and HE-7 showed marked improvement of memory, orientation and reaction. At the same time mental rigidity and trance decreased. Du-20 on its own improved understanding, calculating and social adaptation, while Du-26 was helpful in treating mental retardation, failure to perform daily activities, trance and poor memory. The combination of the three points showed overall the best results in improving intelligence and social adaptation. The particular design of this trial - combining a standard protocol used in both groups with the actually relevant points in the verum group - presents an interesting model for eliminating persistent problems regarding placebo methods and blinding. However, in this particular trial the number of participants (5 groups of 10 subjects) was too low to determine if the results were statistically significant. Lai et Huang, Chin J Integr Med 2005
A German prospective, non-blinded, pair-matched, controlled trial (n=121 pregnant women between 30 and 39 weeks of gestation) investigated the effect of acupuncture at Du-20 and ST-36 on fetal and maternal cardiotocographic parameters and maternal circulation. The main difference was a transient increase of the Fisher score in the treatment group compared to the control group, with a persistent increase of the Fisher score. Scharf et al, Z Geburtshilfe Neonatol 2003
A Croatian prospective, randomised, placebo-controlled trial (n=57) investigated the effectiveness of Du-20, L.I.-4, Ren-3, Ren-4, Ren-6, G.B.-34, BL-23, SP-6 and HE-7 on primary dysmenorrhoea compared to placebo-acupuncture. Subjects were observed for a period of two years. After one year, 93.3% of acupuncture patients were symptom-free and/or not taking medication compared to only 3.7% of the placebo patients. Habek et al, Gynakol Geburtshilfliche Rundsch 2003
A Polish prospective, randomised, controlled, non-blinded trial (n=69) investigated the effect of acupuncture at Du-20, Ren-12, ST-36, ST-21, ST-25, LIV-3, LIV-13, P-6 and HE-7 in addition to a low calorie diet in the treatment of obesity (BMI approximately 33kg/m2). This diet consisted of a daily intake of about 1200-1500kcal, which was about 1000kcal below the daily energy requirement of the patients. The acupuncture group showed a significantly better result after only 12 treatments over a period of 6 weeks. The mean body weight decreased from 85.5kg to 72.7kg, while it only decreased to 77.1kg in the diet group. Wozniak et al, Ginekol Pol 2003
A German prospective, randomised, placebo-controlled, double-blinded trial (n=56) investigated the effect of acupuncture at Du-20, Ex-HN-6, HE-7, P-6 and BL-62 in the treatment of depression and generalised anxiety. Results were assessed using questionnaires. After 10 treatments, the verum acupuncture group showed a significantly larger clinical improvement compared to the placebo group (61% vs 21%). Eich et al, Fortschr Neurol Psychiatr 2000
Urtica dioica (Stinging Nettle)
All parts of the Urtica plant are used as medicine, although only the leaves are used to treat pain. Fresh leaves are used topically for pain as a counterirritant. Urtica leaves are covered with fine hairs with a high silicon content that break when touched and release a toxin into the skin. Like apitherapy, therapeutic effect is achieved by stinging the affected area (urtication). The toxin contains several chemicals including histamine, acetylcholine, and serotonin, and provokes urticaria and C fiber discharge.82
Joint pain: A double-blind, crossover trial of patients with chronic base-of-thumb pain due to osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis found that urtication resulted in decreased disability levels and pain symptoms.83
Dosage: Topical: apply fresh leaf to affected area for approximately 30 seconds two or three times. Repeat as needed.
Mind–Body Therapies
The potential ill effects of mind–body therapies on various body system functions are not well defined or reported. These few reviews, case reports, or studies were published in the English language literature within the last year.
Adverse Effects: Manipulative Therapy, Chiropractic Therapy
A patient with lower back pain undergoing long-term chiropractic care is described as developing “ponytail” syndrome where compression of the roots at the level of the lumbar vertebral canal radiculopathies occurs. The patient recovered after surgical intervention and bladder rehabilitation [49A].
Adverse Effects: Acupuncture
Bee venom, either by bee sting or as diluted venom, is used as part of acupuncture therapy in Asia and other parts of the world. A case of immune thrombocytopenia, including ecchymosis and gum bleeding, is described in an obese 61-year-old woman having bee venom injections weekly to relieve back pain secondary to lumbar disc prolapse. She presented with a large ecchymosis (5 cm) on her abdomen and one on her right forearm (2 cm). Her presenting laboratory values was remarkable for a low platelet count (9 × 109/L) which compared unfavorably to her normal platelet count taken just prior to bee venom treatment (240 × 109/L). Her other laboratory values were not suggestive of any underlying hematologic disorder. Other reports of platelet aggregation inhibition from the venom of bees and wasps led the authors to suspect adverse effect was due to the bee venom therapy [50A].
Adverse Effects: Yoga
Falls resulting from yoga or meditation practices were analyzed in a sub-study analysis of survey data obtained from women aged 59 through 64 years that participated in the Australian Longitudinal Study on Women's Health (ALSWH). Of the entire cohort of 10 011 women completing the survey questionnaire, 4413 (44.1%) had slipped, tripped or stumbled, 2770 (27.7%) women had a fall to the ground, 1398 (14.0%) women had been injured as a result of a fall, and 901 (9.0%) women had sought medical attention for an injury from a fall, within the previous 12 months. Also, yoga or meditation was practiced often by 746 (7.5%) women. Of these reported falls, only four were associated with women who practiced yoga or meditation. A comparison of women who practiced yoga and meditation with those who did not and the fall or injury rate did not show a difference. There was a slight non-statistical advantage of practicing yoga or meditation on reduction of slips, trips or stumbles (OR = 0.92; 95% CI: 0.79–1.08) and the number of times medical attention was sought for injury secondary to a fall (OR = 0.93; 95% CI: 0.70–1.22) during the past 12 months [51M].
Cardiac arrest secondary to heat exhaustion from participating in a “hot” yoga class occurred in a previously healthy 35-year-old woman who was 12 weeks post-partum. CPR was begun promptly at the site. She was placed on vasopressor support. She developed disseminated intravascular coagulation but not hemolysis. Trans-esophageal echocardiogram revealed a mild systolic dysfunction with an ejection fraction of 45%–50% and reduced apical myocardium function. The patient received an implantable cardioverter defibrillator [52r].
Propolis or bee glue
This is the material with which the honey bee seals cracks and crevices, and varnishes surfaces within the hive. Its composition varies according to geographical source. It is collected by worker bees from the leaf buds and is enriched by wounded plant exudates such as mucilages, gums and resins; bee secretions and enzymes are then mixed in. Like honey, the composition varies according to geographical source.
Propolis has a long history, it being used by the Egyptians in the embalming process (antiputrefactive), by the Greeks and Romans in wound treatment (antiseptic), by the Incas (antipyretic) and by inclusion in the London pharmacopoeias of the 17th century. Today it is used by medical herbalists and has become a popular medicament (S. Castaldo and F. Capasso, Fitoterapia, 2002, 73, S1). It also features in apitherapy—an old tradition that has experienced a recent revival.
Over 160 compounds have been shown to be involved and one analysis gave phenolics (58%), beeswax (24%), flavonoids (6%), terpenes (0.5%), lipids and wax (8%) and bioelements, e.g. Mn, Cu, Zn (0.5%). In temperate regions of Europe the resinous coating of poplar buds (Populus nigra, P. italica, P. tremula) forms a major collection source for the bees and the natural phenolic content of the resin, e.g. esters of caffeic and ferulic acids, vanillin, eugenol, flavonoids, etc., can be used to identify the natural source.
Latterly there have been numerous reports concerning the analysis and biological activity of propolis originating from various regions and especially from Latin American countries. In these areas species of Araucaria (Araucariaceae), Baccharis (Compositae) and Clusia (Guttiferae) have been established as biological sources. In addition to the constituents listed previously, prenylated cinnamic acid and chromane derivatives, diterpenoid acids, lignans and components of the volatile oil have been identified.
Notwithstanding the differences in chemical composition of propolis depending on geographical source, a pronounced antibacterial property is common to all. In temperate regions flavonoid and phenolic esters have been shown to exert bacterial activity. New polyisoprenylated benzophenones have recently been reported as antibacterial agents in propolis of Venezuelan origin (B. Trusheva et al., Fitoterapia, 2004, 75, 683), and similar compounds (propolones) have been found in that of Cuban origin together with garcinelliptone and hyperibone (I. M. Hernández et al., J. Nat. Prod., 2005, 68, 931). Neoflavonoids with anti-nitric oxide production activity occur in propolis from Nepal (S. Awale et al., J. Nat. Prod., 2005, 68, 858).
1.7.2 Modern textile architectures and specialised materials with introduced substances
Specialised materials or/and additives with special functions can be introduced in advanced medical textiles. Such special additives can absorb offensive odours from bacteria infected wounds, provide antibacterial properties (silver metals or their salts), include antiseptics, antibacterial constituents, antibiotics, zinc pastes used to sooth pain and relieve irritation, sugar pastes as deodorising agent, provide honey therapy, etc. The integration of therapeutic materials turns textiles into modern medical products. For example, advanced wound care concerns not only the materials covering the outer surface of the body, but also applies to materials like foams, hydrocolloids, hydrogels or matrix materials. Introduction of medical substances into textile structure is developed by immobilisation of medical products upon the polymer.
Gepp et al. (2009) presented the new method and device for encapsulating cells. It is a tool for dispensing very low volumes of ultra high viscosity medical-grade alginate (ALG) hydrogels. Contactless dispensing allows structuring of substrates with ALG, isolation and transfer of cell-alginate complexes as well as the dispensing of biological active hydrogels.
Silver coated fibres with an unchanged textile character are strongly required for several medical applications such as antibacterial and antistatic garments. Of course, for optimal integration into textile production, conductive fibres must allow traditional production processes like weaving, knitting and embroidering, as well as demonstrating high washing fastness. An industry-relevant plasma sputtering process was investigated to improve the mass of the deposited metal for electrical conductivity and the metal–fibre interface for adhesion (Hegemann et al., 2008). Silver-plated polyester (PES) and cotton blended fabrics were determined very effective against bacteria (Jiang et al., 2007). Korner et al. (2008) stated that coatings containing silver were applied to polyester (PES) fabrics. Further applications of such coatings can be found in the fields of textile implants and wound dressings.
Clinical trials have evaluated the efficacy and safety of a new absorbent dressing impregnated with silver salts (Lazareth et al., 2007). As noted by Wang et al. (2007), median number of visits and treatment duration was higher; also the interval between visits was shorter using silver dressing on chronic wounds versus other dressings. Therefore, these results question the effectiveness of silver dressing materials in the management of chronic wounds.
Electrically conductive textiles are increasingly demanded for medical applications, for example, they are very suitable for use as electrodes integrated in electrotherapeutic bandages that stimulate the blood flow in the human body. Schwarz et al. (2008) aimed to create a highly conductive, stable and skin-friendly textile. Gold is an ideal material for this purpose and can be applied in the form of a thin coating of the fabric surface. The para-aramid (AR) multifilaments were coated with a layer of gold. Chemical and electromechanical tests were performed to evaluate the actual mechanism of the formation of the gold layer, and the gold coated para-AR yarns were characterised physically and mechanically.
Propolis
The primary use of propolis has been in immune system enhancement and infections. Propolis has inherent antimicrobial activity that protects the hive block from viruses, bacteria, and other organisms. Propolis has shown considerable antimicrobial activity in in vitro studies.8–10 Propolis also stimulates the immune system, according to preliminary human studies.11,12 In vitro and animal studies have also shown that propolis exerts some antioxidant, liver-protecting, anti-inflammatory, and anticancer properties.13–17
A key use of propolis is protecting against and shortening the duration of the common cold. A preliminary human study reported that propolis extract (PE) reduced upper respiratory infections in children.11 In a double-blind study of 50 patients with the common cold, the group taking PE became symptom-free far more quickly than the placebo group.18
Another possible application of propolis is in the treatment of inflammatory bowel diseases like Crohn disease and ulcerative colitis. An anecdotal article described an interesting case of ulcerative colitis that responded to propolis therapy.19 The author suggested that the antimicrobial and anti-inflammatory properties of propolis might be of value in the treatment of inflammatory bowel diseases.
The antimicrobial properties of propolis may also help protect against parasitical infections in the gastrointestinal tract. One preliminary study of children and adults with giardiasis showed a 52% rate of successful parasite elimination in children and a 60% rate in adults in those given PE (amount not stated).20 However, these results are not as impressive as those achieved with conventional drugs used against giardiasis, so propolis should typically not be used alone for this condition.
Propolis may also have an effect on vaginal infections. In one study, 97 vaginal yeast strains were evaluated for susceptibility to nystatin and PEs. All the yeasts tested were inhibited by low concentrations of PE (maximum of 393.19 mcg/mL of the total flavonoid content), including an isolate resistant to nystatin, regardless of the clinical conditions of the women and the species of yeast isolated.21
Propolis has exerted many positive effects on the oral cavity in clinical studies. This includes its use as a mouthwash, showing benefits in reducing dental plaque22 and gingivitis,23 healing oral wounds,24 improving periodontal pocket depths in type 2 diabetics,25 and reducing the severity and promoting the resolution of oral mucositis associated with chemotherapy.26 In the study on oral mucositis, on day 7 of the study, there were significant differences in the incidence rates of oral wounds, mucositis, and oral cavity erythema between the propolis group and the placebo group, with 65% of the propolis group having complete healing.
Propolis has also been shown to exert some benefit in type 2 diabetes in terms of improvement in blood sugar control, periodontal health, antioxidant activity, and healing of foot ulcers (topical use). However, the degree of absolute improvement in any of these areas is not sufficient on its own. For example, in one double-blind study, a dosage of 900 mg per day of propolis showed statistically significant advantage over the placebo, but after 12 weeks, the fasting blood sugar only dropped from an average of 152 to 134 mg/dL, and the glycosylated hemoglobin A1C only dropped from 8.2% to 7.4%.27 Neither of these improvements reached targeted goals in type 2 diabetes. Similar results were seen in another study using a dosage of 400 mg per day of a propolis product.25 Nonetheless, propolis appears a useful adjunctive therapy for patients with problems with blood sugar control.
Finally, one of the key components of propolis, caffeic acid phenethyl ester, has been shown to exert selective estrogen-receptor modulation.28 This action, along with inhibition of receptor activator nuclear factor-κB ligand (RANKL)-activated signaling, implied that it might be an effective agent against osteoporosis. RANKL is essential for osteoclast differentiation, activation, and survival. Low concentrations of caffeic acid phenethyl ester (<1 mcM) dose-dependently inhibited RANKL-induced osteoclastogenesis in cell and bone marrow macrophage cultures, as well as decreasing the capacity of human osteoclasts to resorb bone.29