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Official websites use. Share sensitive information only on official, secure websites. This research offers an important perspective on the broader goal of incorporating patient and prescriber voices in decision-making. Outcomes included patient information seeking, medication adherence, patient requests for DTCA-promoted prescription drugs, prescribing behaviors, and perceptions of the patient—prescriber relationship and interactions. We searched PubMed and other databases from — and identified 38 studies meeting our study criteria. Of these, 24 studies used patient-reported outcomes and 18 used prescriber-reported outcomes four used both. Most prescribers perceived a neutral influence on the quality of their clinical interactions with patients regarding DTCA. Harms included patients receiving prescriptions for drugs that were not appropriate for them or that the patients did not need, and the potential for DTCA to interfere with medication adherence in some populations, such as those with mental illness. The potential benefits of DTCA on the patient—provider encounter must be balanced with the potential for harms. Direct-to-consumer advertising DTCA of prescription drugs is one of the most common forms of health communication that reaches the U. American adults spend an average of 4. Exposure to DTCA can have both positive and negative effects on health care choices and outcomes. Negative effects include the potential for patients to be misled by communications designed to persuade rather than inform, and overuse of drugs that patients may not necessarily need Almasi et al. Further, it has been suggested that DTCA may have a detrimental effect on the patient—prescriber relationship, undermining the role of the prescriber in prescription drug-related decisions, altering patient expectations for these drugs, and creating pressures to prescribe American College of Physicians, ; Mintzes, ; Robinson et al. Consistent with the growing emphasis among medical and health policy communities on informed and patient-centered decision making, various organizations and funding bodies seek to better understand both the patient and prescriber perspectives on issues related to promotion of medical products Selby, ; U. Thus, assessment of the patient and prescriber perspectives on DTCA is important when considering the larger goal of informed decision making and attention to the patient and prescriber voice. Previous systematic reviews have rigorously evaluated the potential benefits and harms of DTCA on clinical outcomes Gilbody et al. The authors concluded from their reviews that DTCA is associated with increased prescription of advertised products and can have a substantial effect on patient requests for these products. However, due to the strict eligibility criteria, largely absent from these reviews were observational studies that evaluated patient report of health behaviors as a result of DTCA, such as information seeking and medication adherence, or patient perceptions of the content or quality of interactions with physicians surrounding these drugs. We developed our search strategy with consultation from an experienced research librarian as part of a larger investigation on patient and provider perceptions of DTCA. We identified additional studies for inclusion by searching reference lists of seminal studies, forward-tracing relevant studies using Google Scholar and Web of Science, and through consultation with content-area experts. We searched for peer-reviewed English-language studies published between and December We included all research designs and only original research studies conducted in either the United States or New Zealand, because these were the only countries where DTCA was allowed by law at the time of this review. We excluded environmental scans of the literature, editorials, and commentaries. DTCA included marketing or promotional communications delivered through television, print, radio, and web. Based on our preliminary review of the evidence, we identified the following outcomes related to exposure to DTCA for inclusion in our review: patient information seeking from a health care prescriber; patient—prescriber discussions about drugs frequency, content or quality, such as perceptions of the discussion as positive or negative ; patient visits to a health care prescriber; patient and prescriber perceptions of their relationship; patient requests for prescription drugs; prescribing behavior in response to these requests; patient adherence to prescribed drugs. Our focus was on assessments of self-reported behavior and clinical interactions. As such, we excluded studies that did not directly measure patient or prescriber perceptions or their reported behaviors in relation to DTCA e. We excluded studies that measured only behavioral intent e. Our review does not include assessments of over-the-counter drugs. Two members of the research team independently reviewed titles and abstracts and full-text articles against our predefined inclusion and exclusion criteria. A separate senior team member resolved any disagreement about inclusion or exclusion of any specific study. We developed a standardized data abstraction table to collect relevant data from included studies. One member of the team extracted information from each article and a senior team member checked this information for accuracy. We tabulated study characteristics across the body of evidence and synthesized information narratively. Our search results are shown in Figure 1. The electronic database search yielded 1, unduplicated citations and we identified another 40 studies for potential inclusion from manual searches. After removing nonrelevant titles and abstracts, we retained studies for full-text review. Of these, 38 met the inclusion criteria described above. Twenty four studies used patient-reported outcomes and 18 used prescriber-reported outcomes; four used both Aikin et al. Table 1 provides a brief summary of the included 38 studies see Online Appendix B for detailed information on each included study. Thirty-six were cross-sectional surveys; of these, two included patients not exposed to DTCA as a comparison group for analyses. We identified one RCT Kravitz et al. Whereas most of the patient studies surveyed a general population of adults 17 , we identified six studies that focused on patients with specific medical conditions, and three that had a strong focus on either African American or Hispanic populations Allison-Ottey et al. Thirty-one studies assessed the effects of prescription drug DTCA more generally, whereas seven studies assessed the effects of a specific drug type or condition.. Whereas most of the provider studies surveyed only physicians 17 , four studies surveyed other prescribers e. Sample characteristics ranged from small, convenience samples of single-practice sites to random samples drawn from large prescriber membership databases. We organize our findings below first by patient versus prescriber-reported outcomes. Within each major grouping, we further organize our findings by the outcome of interest. Due to space constraints, we largely focus our discussion on studies with either large, population-based samples or those with more rigorous designs. Patients reported that DTCA prompted them to seek more information from health care professionals about a condition or drug or have discussions about them in 22 studies Online Supplement Appendix C. For example, a large, national survey conducted by the U. Very rarely did patients report that DTCA was the sole reason for scheduling a medical visit Aikin et al. Two of the four studies that assessed this outcome were conducted with large, national samples Aikin et al. The same survey found that those with lower education levels, who had chronic disease, and who were Hispanic were more likely to schedule an appointment for preventive care or a checkup as a result of DTCA. More commonly, patients reported that, during a medical appointment they had already scheduled, they discussed a condition or drug depicted in DTCA. Eighteen studies reported on patient requests for prescription drugs and related outcomes, such as receipt of new prescriptions and medication change as a result of DTCA Online Supplement Appendix C. The frequencies in which these outcomes occurred varied widely across studies Here, we discuss the study findings from four large, probability-based surveys. More than half of respondents in the previously described study by Murray and colleagues reported having requested at least one medical intervention from their physicians as a result of DTCA; most requests were for changes in medications, followed by tests and referrals to specialists for conditions that were described in the DTCA. This outcome was more common in white patients and those with higher socioeconomic status. However, an important question not addressed in the body of research identified in our review is whether new drugs prescribed as a result of DTCA were appropriate the patient was treated for an overlooked condition or received symptom relief for an existing condition or if they resulted in overprescribing and overtreatment of the patient. Although this finding suggests that DTCA may be a possible risk factor for medication nonadherence, it is unclear if this finding can be generalized to other patient populations and medical conditions. Findings from seven studies reporting on patient perceptions of the patient—prescriber relationship as a result of exposure to DTCA were mixed Online Supplement Appendix C. Respondents who requested a specific drug but did not receive it were more likely to report a worsened relationship. Findings from studies with local samples yielded similarly mixed results with regard to the extent to which DTCA improved the patient-provider relationship Huh et al. Reports regarding prescribing behavior as a result of DTCA-prompted requests from patients varied across studies and measures Online Supplement Appendix D. In the above-mentioned assessment of 1, clinical encounters in a Colorado health network, requests for prescription drugs prompted by DTCA were very uncommon, occurring in only 3. Further, these inquiries were more frequent in the community clinic samples than in the private clinic samples 7. Other studies assessed perceived pressures to prescribe and yielded varying responses Aikin et al. The study did not evaluate whether the changes in prescribing were medically appropriate. Two studies suggest that DTCA-prompted requests for prescriptions can have profound influence on prescriber behavior. Mintzes and colleagues conducted on-site surveys of patient and physician pairs in a clinic in the United States U. The design was advantageous in that the setting minimized potential influence of recall bias and the pairing of patient and physician responses allowed for a more nuanced evaluation of this topic. After the clinical encounters, physicians in this study were asked to reflect on these requests and rate the likeliness unlikely, possibly, very likely of prescribing the drug for other similar patients. In a randomized trial by Kravitz and colleagues , trained actors posing as patients with fictitious symptoms made requests to primary care physicians for antidepressants for either major depressive disorder or adjustment disorder, the latter being a condition for which antidepressants are not clinically approved. Thus, DTCA-prompted requests addressed underuse by appropriately diagnosing and prescribing for those with major depression, but also promoted overuse by providing inappropriate prescriptions for those with adjustment disorder. Follow-up focus groups with 22 of the surveyed physicians pointed to a tendency to err toward overtreatment to build better rapport when faced with a potentially stigmatizing condition Tentler et al. Adverse outcomes included lengthening clinic times to correct misperceptions or explain why a requested drug was inappropriate or an alternative drug was better Bhanji et al. We focus our discussion on key gaps in the literature and areas for future exploration. Whereas the preponderance of the literature we identified studied exposure to DTCA more generally, fewer studies explored the influence of DTCA on specific disease conditions. Our review identified no studies on patient and provider perceptions of DTCA-related behaviors outside of mental illness or anxiety disorders, signaling a gap in the literature. Findings from studies in the context of mental health suggested that DTCA can influence requests for and prescribing of these medicines. Further, in one well-designed study, exposure to DTCA was associated with decreased adherence to mental health medications noteworthy in this study was the inclusion of a comparison group of patients who reported not having been exposed to DTCA for these drugs. Our review also suggests that the literature on DTCA and health-related behavior is dated; about three-quarters of the studies identified in our review were more than a decade old. Given the changing landscape of DTCA, where patients are increasingly exposed to online prescription drug promotion on pharmaceutical websites or through interactive social media including drug company—sponsored Facebook pages, Twitter accounts, and YouTube channels, for example , further exploration within this new and rapidly changing era of online promotion is warranted. Other limitations to the research we identified were that studies seldom included a meaningful comparison group e. Therefore, it is difficult to know if the frequency with which patients reported outcomes would have been higher or lower among those not exposed to DTCA. Second, studies often asked patients to recall past behaviors, which is prone to recall bias. Stronger research designs assessed patient and prescriber reactions to DTCA at the time of actual clinical encounters.. Assessments of diverse samples, including those with lower educational backgrounds or those who speak English as a second language, were rare; these groups warrant further study because they may be highly influenced to the information presented in DTCA. Finally, many of the conclusions drawn from this literature assume a somewhat simplistic model of behavior change, where exposure to DTCA is thought to influence thought, which in turn leads to behavior. For example, exposure to DTCA may have a stronger influence for some population segments e. A more nuanced understanding of how and for whom DTCA exerts its influence would aid the field moving forward. Our review methodology had some limitations. Our search found that studies addressing this topic were not indexed in a consistent way; thus, our review may have missed some relevant studies. However, we mitigated this possibility through an extensive backward and forward hand-search process, as described in our methods. We did not conduct a formal quality assessment of the studies in our review, so we cannot evaluate the strength of this body of evidence. Finally, our review is limited by publication bias and thus may overstate the benefits or harms of DTCA exposure. Our literature review echoes many of the conclusions made in previous studies about the reported benefits and harms of DTCA on health-related behaviors. Additional research is needed that assesses the influence on specific disease conditions such as the influence of DTCA on cancer-related decision-making ; uses strong observational designs e. The authors have indicated they have no financial relationships relevant to this article to disclose. Broad use of this term does not imply endorsement by FDA. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Health Commun. Published in final edited form as: Health Commun. Find articles by Jessica T DeFrank. Find articles by Nancy Berkman. Find articles by Leila Kahwati. Find articles by Katherine Cullen. Find articles by Kathryn J Aikin. Find articles by Helen W Sullivan. Issue date May. PMC Copyright notice. The publisher's version of this article is available at Health Commun. Open in a new tab. Summary of Included Studies 2. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Specific drug type or set of types or condition.

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Systemic Lupus Erythematosus SLE is a chronic autoimmune systemic disease with a wide range of clinical symptoms, complex development processes, and uncertain prognosis. The clinical treatment of SLE is mainly based on hormones and immunosuppressants. Research on novel therapy strategies for SLE has flourished in recent years, especially the emergence of new targeted drugs and natural products that can modulate related symptoms. This review discusses the current experience including B-cell targeted drugs belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab , T-cell targeted drugs abatacept, dapirolizumab, and inhibitor of syk and CaMKIV , cytokines targeted drugs anifrolumab and sifalimumab , and natural products curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol. The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers. SLE is a complex autoimmune inflammatory disease with a diverse course and prognosis that can involve multiple organs throughout the body. It mostly affects women, and its clinical symptoms range from mild to life-threatening. This clinical heterogeneity is most likely caused by intricate immunological dysregulation, like the loss of immunological tolerance to autoantigens and the development of multiple autoantibodies Bentham et al. Immune complexes formed by autoantibodies binding to intracellular autoantigens are deposited in the skin, blood vessels, kidneys, and liver. Over time, these immune complexes will cause tissue damage and the emergence of a variety of diseases or manifestations, such as zygomatic rash, arthralgia, fever, renal failure, and cardiovascular disease Fava and Petri, ; Herrada et al. It may have a negative impact on the life quality and long-term prognosis of SLE patients Davidson, The disease cannot be cured for now, but its progression can be controlled by early diagnosis and medications. However, conventional treatments are accompanied by significant side effects and ideal treatment options are rare. The anti-inflammatory effects of these medicines are accompanied by adverse effects caused by the toxic effects of the drug, including cataracts, osteoporotic fractures, cardiovascular injury, severe infections, malignancies, teratogenicity, and infertility, potentially leading to additional organ damage and mortality Curtis et al. Therefore, The medical community is eager for safer treatment profiles and more targeted therapies. Fortunately, an increasing number of studies have focused on exploring new drugs and therapies and found that targeted drugs and natural products offer significant therapeutic promise in the treatment of SLE. Due to the low specificity and adverse effects of traditional therapeutic agents, there is still some unmet need for more targeted agents with better safety profiles in SLE treatment. Based on recent advances in understanding the complex pathogenesis of SLE, several targeted therapies are presently being evaluated in clinical trials. A wealth of evidence points to B cells as key players in the pathogenesis of SLE. B cells initiate self-reactive T cells, such as antigen-presenting cells, to release pro-inflammatory cytokines and chemokines, promote the generation of autoimmune responses in target organs, and are considered as potential targets for SLE therapy Table 1 Sanz and Lee, ; Tsokos et al. Belimumab, a fully humanized anti-BAFF monoclonal antibody, has been the first biologic drug to receive a license for the treatment of SLE to date. In the RCT, this medicine was shown to be effective in reducing SLE disease activity and severe flares and delaying the onset of lupus in addition to standard therapy Furie et al. And according to the findings of a prospective cohort trial, belimumab may have clinical benefits for people with acute and subacute cutaneous lupus erythematosus by decreasing the frequency of flares and slowing the progression of skin lesions in patients with active SLE Iaccarino et al. In a week trial conducted at sites in 21 countries, the probability of kidney-related events, morbidity, and mortality was all lower in the trial group compared to the control group, which demonstrates the utility of belimumab with standard therapy Furie et al. The effectiveness, safety, and pharmacokinetics of intravenous belimumab were assessed in a Phase-2, randomized, placebo-controlled, double-blind research for children with systemic lupus erythematosus cSLE. The results show that belimumab was well tolerated by paediatric patients, and the pharmacokinetics, pharmacodynamics and safety profiles were similar to those of adults with SLE Brunner et al. A week open-label study found that increases occurred in the proportions of patients achieving primary efficacy renal response and complete renal response from open-label baseline to week Additionally, no new safety signals were identified, and efficacy was generally maintained throughout the open-label phase Furie et al. The results of randomized, double-blind phase 1a and phase 1b trials demonstrated that the safety and tolerability profile of blisibimod in SLE was comparable with that of placebo Stohl et al. In this RCT, SLE responder index 5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo; however, reductions in proteinuria, changes in anti-double standard DNA antibody, complement C3 and C4, and reductions in B cells were observed significantly with blisibimod Furie et al. Although the SLE responder index 6 was not met in the study, blisibimod was well-tolerated and was associated with steroid reduction, decreased proteinuria and biomarker responses Merrill et al. The results of the study showed that there was a trend toward an improved SLE responder index 4 response rate with atacicept 75 mg and mg as compared with placebo. Additionally, the risk of serious adverse events and serious or severe infection was not increased with atacicept as compared with placebo Merrill et al. Additionally, patients on continuous mg atacicept had a reduced risk of first severe flare and a longer time to first severe flare. The study has drawn the conclusion that long-term treatment with atacicept mg in SLE patients had an acceptable safety profile and durable efficacy Wallace et al. CD20 is a cell-surface antigen expressed on most B cells, except plasma cells, the majority of plasmablasts, and lymphoid stem cells Gelfand et al. For the treatment of SLE, the combination of RTX and belimumab has undergone substantial research and appears to be a valuable potion for several clinical situations. In this study, patients were treated with RTX and then 4—8 weeks later were randomized to receive belimumab or placebo for 52 weeks. The result of this study showed that belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced the risk of severe flare in SLE patients who are refractory to conventional therapy at 52 weeks Shipa et al. The efficacy of the combination of RTX and belimumab is theoretically plausible but requires more clinical studies and case reports to confirm it. Ofatumumab is a fully humanized anti-CD20 monoclonal antibody and is a safe, well-tolerated and effective alternative for B cell depletion Cinar et al. Ofatumumab has recently received permission for treatment in individuals with chronic lymphocytic leukemia Sandhu and Mulligan, and multiple sclerosis Hauser et al. In this study, B cell depletion was achieved in 12 patients and was associated with improvement in serological markers of disease activity including ANA, anti-dsDNA antibody, and complement levels. Additionally, half of the patients with LN achieved renal remission by 6 months Masoud et al. Therefore, ofatumumab has been used and resulted in marked clinical improvement in both patients Lei et al. A study of single-center retrospective case series for juvenile SLE found that significant clinical improvement was observed in all cases after using ofatumumab, mirrored by improved laboratory markers of disease activity including anti-dsDNA antibody, complement levels, and proteinuria Cinar et al. Ocrelizumab is another fully humanized anti-CD20 antibody. Anyhow, initial results suggested ocrelizumab may have some efficacy in treating LN. CD19 is a transmembrane protein on the surface of B lymphocytes and is an important co-receptor for B cell antigen receptor BCR signaling. It is closely related to the activation, signal transduction, and growth of B cells. CD19 co-linked with BCR synergistically enhances calcium release, mitogen-activated protein kinase activity and cell proliferation Li et al. CD19 has been widely used in the diagnosis and prognosis of leukemia, lymphoma, and immune system diseases, and is an important target for immunotherapy. CD22 is expressed in mature B cells and modulates activation and migration of B cells by acting as an inhibitory co-receptor of the B-cell receptor. Epratuzumab is a humanized antibody binding to the glycoprotein CD22 of the cell surface of mature B cells Clowse et al. An open-label extension study indicated that open-label epratuzumab treatment was well tolerated for up to 3. This result has been confirmed in several other studies Strand et al. Studies have shown that the production of anti-DNA antibodies and other pathogenic autoantibodies in SLE patients or mice is T-cell dependent Comte et al. SLE has multiple T-cell abnormalities, and the activation of auto-reactive T lymphocytes and the resulting autoimmune responses are central to the occurrence of the disease Yasutomo, Abatacept is a fusion protein composed of cytotoxic T-associated protein 4 CTLA-4 a leukocyte differentiation antigen and the Fc region of IgG1 an immunoglobulin fused to extracellular structures. Two signals are required for T cells to activate and attack antigens to produce an immune response. For the first signal, antigen-presenting cells APCs bind to major histocompatibility complex MHC molecules and be presentd to T cell receptors on the T cell surface; for the second signal, APCs present B7 protein on their cell surface to CD28 protein on the T cell surface. Abatacept binds to B and B and blocks the signaling 2 pathway, preventing T cells from being activated. In another clinical trial, a total of patients were treated for 52 weeks to compare the efficacy and safety of intravenous IV abatacept. These unsatisfactory results may be related to a flawed study design that requires continuous optimization at a later stage. The safety profile of abatacept in patients with SLE suggests that abatacept may be considered as an alternative in refractory cases. Interaction between the CD40 ligand CD40L, CD; mainly expressed on activated T cells and platelets and the CD40 receptor expressed on a variety of cells, including antigen-presenting cells and B cells is essential for the activation of the adaptive immune system and drive the pathological process in SLE, including B cell differentiation and proliferation Furie et al. The first study showed predictable pharmacokinetics in both healthy individuals and patients with SLE and was well tolerated, with no safety signals of concern Tocoian et al. The second study showed that multiple doses of dapirolizumab were well-tolerated, and there were no thromboembolic events during the study Chamberlain et al. The result of the study showed that although the primary objective was not met, dapirolizumab appeared to be well tolerated, and patients exhibited improvements across multiple clinical and immunological measures of disease activity after 24 weeks relative to placebo Furie et al. Further research is necessary to determine the clinical benefit of dapirolizumab. Syk is implicated in membrane-mediated signal transduction in a variety of cells and overexpressed in T cells of patients with SLE Krishnan et al. Syk inhibitor also decreased the growth of spleen and lymph nodes and inhibited kidney disease progression Deng et al. Anifrolumab, a monoclonal antibody that targets the type I IFN receptor, successfully treated individuals with SLE in a phase 3 randomized trial in Morand et al. The results showed that adverse events in patients in the anifrolumab group included respiratory infections, nasopharyngitis, and infusion-related reactions. The number of adverse outcomes was lower than that in the placebo group, as well as better GC tapering and severity of skin disease than with the placebo Morand et al. Although the result showed that the primary endpoint was not met, anifrolumab intensified regimen was associated with numerical improvements over the placebo acrossing endpoint, including complete renal response CRR , urine protein-creatinine ratio, CRR with inactive urinary sediment, and sustained glucocorticoid reductions Jayne et al. Still, more studies are required to confirm the effectiveness and safety of this drug. A recent phase II b clinical trial demonstrated that Sifalimumab has an inhibitory effect on IFN gene expression in patients with moderately to severely active SLE, resulting in remission of disease activity and joint injury Takeuchi et al. Therefore, it is important to further explore the role of the type I IFN signaling pathway in autoimmune diseases to develop more effective and safe therapies approaches. The pathogenesis of SLE is still unclear, and multi-level analysis of relevant cytokines is beneficial to provide a basis for new target therapy for SLE in the future. Numerous studies in recent years have revealed that natural products derived from animals and plants are effective in healing human diseases. Nature products showed promising further therapeutic effects in vitro and in vivo models of SLE through various mechanisms Figure 2 , as shown in Table 2. The mechanisms of nature products in the treatment of SLE are diverse and complex, which urgently need to be summarized and analyzed. TABLE 2. The major effects of natural products in vitro and in vivo models of SLE. Ginger is thought to have anti-inflammatory and antioxidant effects, and the health-promoting properties of ginger have been attributed to its rich phenolic phytochemicals, such as curcumin CUR Jolad et al. CUR, a phenolic component extracted from turmeric, belongs to the ginger family and has been shown to have immunomodulatory and anti-inflammatory effects in various diseases Chamani et al. According to animal reseatch, CUR has the potential to cure a wide range of inflammatory diseases Aggarwal and Harikumar, Although immunotherapy considerably improves the prognosis of patients with SLE and nephropathy, several patients with LN eventually get end-stage renal disease Faurschou et al. Proline-rich tyrosine kinase 2 PYK2 is a non-receptor protein tyrosine kinase belonging to the superfamily of adhesion kinases. It plays a significant role in the development of autoimmune disorders and delivers critical signals during lymphocyte activation Sasaki et al. According to in vitro research, CUR can inhibit the proliferation of peripheral blood mononuclear cells in LN patients by suppressing the expression and activation of PYK2. Additionally, CUR inhibition showed a negative correlation with complement levels in the serum and positive correlation with proteinuria levels measured after 24 h, without affecting normal subjects Wang et al. Although CUR has potential therapeutic value for SLE, its poor bioavailability limits its therapeutic effect due to poor absorption, rapid metabolism, and rapid systemic elimination Anand et al. One study found that reconstituting CUR with a non-curcumin-like component of turmeric can greatly improve the bioavailability of turmeric Antony et al. An RCT study was taken to evaluate the effect of turmeric and the result showed that proteinuria, systolic blood pressure and hematuria decreased significantly in SLE patients after received capsules that contained turmeric for 3 months Khajehdehi et al. Oleuropein OL is key to the main anti-inflammatory action of olive leaf extract and has a pharmacologically important antioxidant, anti-inflammatory, and immunomodulatory properties Ryu et al. Peracetylated oleuropein Per-OL are acyl derivatives of OL and have the potential to protect membrane components due to their lipophilic nature, which enables them to cross cytoplasmic cell membranes and be taken up by cells. This results in better absorption through intestinal epithelial cell monolayers than OL Stamatopoulos et al. OL and Per-OL can significantly reduce renal injury and serum matrix metalloproteinase-3 and prostaglandin E2 levels. Punicalagin PCG , a major polyphenol-rich in pomegranate, has antioxidant, anti-inflammatory, and immunosuppressive effects Venusova et al. Studies have shown that PCG can effectively inhibit protease-activated receptor-2 PAR2 , which is abundantly expressed in human tissues, particularly in renal cells, such as podocytes, thylakoid cells, tubular epithelial cells and infiltrating immune cells Vesey et al. Sulforaphane SFN , found in cruciferous plants, is an activator of NRF2 and has several biological properties that may lower the risk of developing chronic diseases, such as anti-inflammatory, antioxidant, and anti-tumor activities Raiola et al. Previous research suggests that Nrf2 deficiency increases the development of LN, revealing a preventative or protective role for SFN. Experimental data have demonstrated the significance of anti-oxidative stress and the NF-kB pathway in lupus in a mouse model of LN Jiang et al. Th1 and Th17 cells expressed more and lived longer after receiving SFN therapy. The proportion of plasma cells, T follicular helper Tfh cells, neutrophils, dendritic cells, and quantity of malondialdehyde all decreased. The above studies also suggest that antioxidant therapy may be a potential approach to treating SLE. Icariin ICA is recognized as a traditional herb in eastern Asia, which benefits osteoporosis, chronic nephritis, asthma, hepatitis, and cardiovascular disease. ICA is the most abundant flavonol glycoside in Epimedium. It has a range of therapeutic effects, including anti-inflammatory, antioxidant, anti-cancer, and anti-aging properties Li et al. Flavonoids have various biological benefits include free radical scavenging, antioxidant, anti-inflammatory, and anti-cancer. Based on in vivo , and clinical trial studies, API is a potential therapeutic agent. This compound has the ability to reduce PG synthesis, nitric oxide generation, and the activity of numerous enzymes that control cell growth Kasiri et al. The results showed that API inhibited the response of Th1, Th17 cells, and B cells to major lupus autoantigens by suppressing autoantigen presentation and the value-added function of APCs. Resveratrol RES is a molecule known chemically as 35,4-trihydroxystilbene. It is a natural plant antitoxin that can be synthesized from various plants, including grapes, wine, soy, nuts, and chocolate, and is produced in pathogenic and stressful environments Oliveira et al. The molecule can be distributed into tissues by reversible interaction with serum albumin by its cis-trans isomeric Tang et al. Treatment of pristane-induced lupus mice with different doses of RES has been shown to reduce proteinuria, renal immunoglobulin deposition, glomerulonephritis, and serum IgG1 and IgG2a levels. In in vitro, antibody production and B-cell proliferation were also inhibited. Also, the data showed that RES inhibited cholesterol efflux in macrophages Voloshyna et al. A study was taken to evaluate the combinatorial effect of RES and piperine on the murine model. Renal manifestations proteinuria and decreased creatinine in urine were successfully mitigated by the combination of RES and piperine Pannu and Bhatnagar, The study demonstrated that RES could potentially be a therapeutic candidate in the modulation of cognitive dysfunction in neuropsychiatric lupus, especially motor incoordination. Kasselman et al. RES also has some limitations. Its metabolism in in vivo is rapid and its bioavailability is limited Walle, ; Pujara et al. It also shows some mild toxic effects at high doses of treatment, such as headache, lower extremity myalgia, drowsiness, blood electrolyte changes, and rash Cottart et al. Therefore, its bioavailability and toxicity should be taken into account when considering its possible therapeutic effects. In this review, we enumerate the great potential of antibody drugs and natural medicines in the treatment of SLE. Despite the great therapeutic value of targeted and natural drugs, there are still some limitations in the treatment of autoimmune diseases. Therefore, every effort should be made to develop safer and more effective therapies, develop treatment regimens that rapidly control lupus activity, prevent future relapses, and prevent additional short-term and long-term complications. YH: writing—original draft, data charting, and data collation. LL: data collation. BZ: data collation. RL: data collation. XZ: data collation. BL: revising-orginal draft. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Aggarwal, B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Almaani, S. Update on lupus nephritis. Anand, P. Bioavailability of curcumin: Problems and promises. Anders, H. Lupus nephritis. Antony, B. A pilot cross-over study to evaluate human oral bioavailability of BCMcg biocurcumax , A novel bioenhanced preparation of curcumin. Indian J. Apostolopoulos, D. It hasn't gone away: The problem of glucocorticoid use in lupus remains. Bag-Ozbek, A. Emerging B-cell therapies in systemic lupus erythematosus. Risk Manag. Bauer, J. Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation study. Arthritis Rheum. Bentham, J. 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Advances in natural products and antibody drugs for SLE: new therapeutic ideas. TABLE 1. B-cell-targeted investigation for treatment of SLE. Mechanism of targeted drugs in the treatment of SLE. Chemical formulas for natural products effective in the treatment of SLE.

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